CN109053901A - 血脑屏障穿梭体 - Google Patents
血脑屏障穿梭体 Download PDFInfo
- Publication number
- CN109053901A CN109053901A CN201810972126.3A CN201810972126A CN109053901A CN 109053901 A CN109053901 A CN 109053901A CN 201810972126 A CN201810972126 A CN 201810972126A CN 109053901 A CN109053901 A CN 109053901A
- Authority
- CN
- China
- Prior art keywords
- blood
- brain
- brain barrier
- entity
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000008499 blood brain barrier function Effects 0.000 title claims abstract description 205
- 210000001218 blood-brain barrier Anatomy 0.000 title claims abstract description 204
- 210000004556 brain Anatomy 0.000 claims description 151
- 230000027455 binding Effects 0.000 claims description 89
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 69
- 239000012636 effector Substances 0.000 claims description 63
- 150000001413 amino acids Chemical group 0.000 claims description 62
- 239000003814 drug Substances 0.000 claims description 59
- 210000004027 cell Anatomy 0.000 claims description 57
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 claims description 55
- 108050003222 Transferrin receptor protein 1 Proteins 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 50
- 102000005962 receptors Human genes 0.000 claims description 48
- 108020003175 receptors Proteins 0.000 claims description 48
- 201000010099 disease Diseases 0.000 claims description 46
- 229940079593 drug Drugs 0.000 claims description 31
- 108020001507 fusion proteins Proteins 0.000 claims description 31
- 102000037865 fusion proteins Human genes 0.000 claims description 31
- 108090000623 proteins and genes Proteins 0.000 claims description 31
- 208000012902 Nervous system disease Diseases 0.000 claims description 30
- 208000025966 Neurological disease Diseases 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 30
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 23
- 102000004169 proteins and genes Human genes 0.000 claims description 23
- 210000004369 blood Anatomy 0.000 claims description 21
- 239000008280 blood Substances 0.000 claims description 21
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 17
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 14
- 230000004888 barrier function Effects 0.000 claims description 14
- 239000003900 neurotrophic factor Substances 0.000 claims description 14
- 102000004190 Enzymes Human genes 0.000 claims description 13
- 108020004707 nucleic acids Proteins 0.000 claims description 13
- 102000039446 nucleic acids Human genes 0.000 claims description 13
- 150000007523 nucleic acids Chemical class 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 11
- 239000003102 growth factor Substances 0.000 claims description 9
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- 239000002254 cytotoxic agent Substances 0.000 claims description 8
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 8
- 239000012634 fragment Substances 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
- 102000000853 LDL receptors Human genes 0.000 claims description 7
- 108010001831 LDL receptors Proteins 0.000 claims description 7
- 102100022205 Tumor necrosis factor receptor superfamily member 21 Human genes 0.000 claims description 7
- 101710187751 Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 claims description 7
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052737 gold Inorganic materials 0.000 claims description 7
- 239000010931 gold Substances 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims description 6
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims description 6
- 108091000054 Prion Proteins 0.000 claims description 5
- 102000004584 Somatomedin Receptors Human genes 0.000 claims description 5
- 108010017622 Somatomedin Receptors Proteins 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 5
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 claims description 4
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 claims description 4
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 claims description 4
- 102100029470 Apolipoprotein E Human genes 0.000 claims description 4
- 101710095339 Apolipoprotein E Proteins 0.000 claims description 4
- 101800003838 Epidermal growth factor Proteins 0.000 claims description 4
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 4
- 102000003746 Insulin Receptor Human genes 0.000 claims description 4
- 108010001127 Insulin Receptor Proteins 0.000 claims description 4
- 102000011931 Nucleoproteins Human genes 0.000 claims description 4
- 108010061100 Nucleoproteins Proteins 0.000 claims description 4
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims description 4
- 229940116977 epidermal growth factor Drugs 0.000 claims description 4
- 229960002897 heparin Drugs 0.000 claims description 4
- 229920000669 heparin Polymers 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 230000026731 phosphorylation Effects 0.000 claims description 4
- 238000006366 phosphorylation reaction Methods 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 230000003252 repetitive effect Effects 0.000 claims description 4
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 3
- 108091000080 Phosphotransferase Proteins 0.000 claims description 3
- 108010036908 Presenilin-2 Proteins 0.000 claims description 3
- 230000010005 growth-factor like effect Effects 0.000 claims description 3
- 102000020233 phosphotransferase Human genes 0.000 claims description 3
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 claims description 2
- 102000004018 Caspase 6 Human genes 0.000 claims description 2
- 108090000425 Caspase 6 Proteins 0.000 claims description 2
- 102000002322 Egg Proteins Human genes 0.000 claims description 2
- 108010000912 Egg Proteins Proteins 0.000 claims description 2
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 claims description 2
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 claims description 2
- 235000014103 egg white Nutrition 0.000 claims description 2
- 210000000969 egg white Anatomy 0.000 claims description 2
- 210000000225 synapse Anatomy 0.000 claims description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 claims 3
- 102000009024 Epidermal Growth Factor Human genes 0.000 claims 2
- 102000011965 Lipoprotein Receptors Human genes 0.000 claims 1
- 108010061306 Lipoprotein Receptors Proteins 0.000 claims 1
- 102000012419 Presenilin-2 Human genes 0.000 claims 1
- 102000029797 Prion Human genes 0.000 claims 1
- 231100000167 toxic agent Toxicity 0.000 claims 1
- 239000003440 toxic substance Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 29
- 206010010904 Convulsion Diseases 0.000 description 30
- 238000004043 dyeing Methods 0.000 description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 29
- -1 small molecule compound Chemical class 0.000 description 27
- 235000001014 amino acid Nutrition 0.000 description 26
- 229940024606 amino acid Drugs 0.000 description 26
- 239000000427 antigen Substances 0.000 description 25
- 108091007433 antigens Proteins 0.000 description 25
- 102000036639 antigens Human genes 0.000 description 25
- 238000011282 treatment Methods 0.000 description 25
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 22
- 239000002953 phosphate buffered saline Substances 0.000 description 22
- 235000018102 proteins Nutrition 0.000 description 22
- 108060003951 Immunoglobulin Proteins 0.000 description 20
- 102000018358 immunoglobulin Human genes 0.000 description 20
- 210000002889 endothelial cell Anatomy 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 16
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 16
- 239000001961 anticonvulsive agent Substances 0.000 description 16
- 238000002347 injection Methods 0.000 description 16
- 239000007924 injection Substances 0.000 description 16
- 208000011580 syndromic disease Diseases 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 15
- 239000000872 buffer Substances 0.000 description 15
- 229940124597 therapeutic agent Drugs 0.000 description 15
- 239000011521 glass Substances 0.000 description 14
- 238000005259 measurement Methods 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 12
- 101100369221 Mus musculus Tfrc gene Proteins 0.000 description 12
- 239000000975 dye Substances 0.000 description 12
- 230000004927 fusion Effects 0.000 description 12
- 102100026376 Artemin Human genes 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 208000024827 Alzheimer disease Diseases 0.000 description 10
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 10
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 10
- 229960000074 biopharmaceutical Drugs 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 206010002022 amyloidosis Diseases 0.000 description 9
- 206010015037 epilepsy Diseases 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 230000002792 vascular Effects 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 8
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 8
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 8
- 239000004471 Glycine Substances 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 8
- 231100000135 cytotoxicity Toxicity 0.000 description 8
- 230000003013 cytotoxicity Effects 0.000 description 8
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 8
- 229960004679 doxorubicin Drugs 0.000 description 8
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 8
- 229940124530 sulfonamide Drugs 0.000 description 8
- BYJAVTDNIXVSPW-UHFFFAOYSA-N tetryzoline Chemical compound N1CCN=C1C1C2=CC=CC=C2CCC1 BYJAVTDNIXVSPW-UHFFFAOYSA-N 0.000 description 8
- 230000032258 transport Effects 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 208000015439 Lysosomal storage disease Diseases 0.000 description 7
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000006471 dimerization reaction Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 150000003384 small molecules Chemical class 0.000 description 7
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 6
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 229930192392 Mitomycin Natural products 0.000 description 6
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Chemical compound CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 6
- 230000006399 behavior Effects 0.000 description 6
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 238000004624 confocal microscopy Methods 0.000 description 6
- 229960000975 daunorubicin Drugs 0.000 description 6
- 229960003529 diazepam Drugs 0.000 description 6
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 6
- 229960000520 diphenhydramine Drugs 0.000 description 6
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 6
- 238000013507 mapping Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 6
- 229960004857 mitomycin Drugs 0.000 description 6
- 229960001156 mitoxantrone Drugs 0.000 description 6
- 229960005016 naphazoline Drugs 0.000 description 6
- 229960001699 ofloxacin Drugs 0.000 description 6
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 6
- 229960005205 prednisolone Drugs 0.000 description 6
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 239000013049 sediment Substances 0.000 description 6
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 6
- 229960003946 selegiline Drugs 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 229960005294 triamcinolone Drugs 0.000 description 6
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 6
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 5
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 5
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 5
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 5
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 5
- 108010000817 Leuprolide Proteins 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 208000001089 Multiple system atrophy Diseases 0.000 description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 5
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 5
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 5
- 229960003644 aztreonam Drugs 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 229960004630 chlorambucil Drugs 0.000 description 5
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 5
- 229960001076 chlorpromazine Drugs 0.000 description 5
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 5
- 229960003120 clonazepam Drugs 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 5
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 5
- 229960005420 etoposide Drugs 0.000 description 5
- 235000008191 folinic acid Nutrition 0.000 description 5
- 239000011672 folinic acid Substances 0.000 description 5
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 5
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical class NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 229960001691 leucovorin Drugs 0.000 description 5
- 235000018977 lysine Nutrition 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 201000006938 muscular dystrophy Diseases 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 229960005333 tetrabenazine Drugs 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 239000003656 tris buffered saline Substances 0.000 description 5
- 229960004528 vincristine Drugs 0.000 description 5
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 5
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 5
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 description 4
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 4
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 4
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 4
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 239000012099 Alexa Fluor family Substances 0.000 description 4
- 102100034452 Alternative prion protein Human genes 0.000 description 4
- QTGIAADRBBLJGA-UHFFFAOYSA-N Articaine Chemical compound CCCNC(C)C(=O)NC=1C(C)=CSC=1C(=O)OC QTGIAADRBBLJGA-UHFFFAOYSA-N 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 206010003628 Atonic seizures Diseases 0.000 description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 108010006654 Bleomycin Proteins 0.000 description 4
- 201000006474 Brain Ischemia Diseases 0.000 description 4
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 4
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 4
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- 229930182566 Gentamicin Natural products 0.000 description 4
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 4
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 4
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 4
- 206010021750 Infantile Spasms Diseases 0.000 description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 4
- 208000005870 Lafora disease Diseases 0.000 description 4
- 208000014161 Lafora myoclonic epilepsy Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 229930193140 Neomycin Natural products 0.000 description 4
- 102000015336 Nerve Growth Factor Human genes 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- UOZODPSAJZTQNH-UHFFFAOYSA-N Paromomycin II Natural products NC1C(O)C(O)C(CN)OC1OC1C(O)C(OC2C(C(N)CC(N)C2O)OC2C(C(O)C(O)C(CO)O2)N)OC1CO UOZODPSAJZTQNH-UHFFFAOYSA-N 0.000 description 4
- MFOCDFTXLCYLKU-CMPLNLGQSA-N Phendimetrazine Chemical compound O1CCN(C)[C@@H](C)[C@@H]1C1=CC=CC=C1 MFOCDFTXLCYLKU-CMPLNLGQSA-N 0.000 description 4
- KCLANYCVBBTKTO-UHFFFAOYSA-N Proparacaine Chemical compound CCCOC1=CC=C(C(=O)OCCN(CC)CC)C=C1N KCLANYCVBBTKTO-UHFFFAOYSA-N 0.000 description 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
- 208000006289 Rett Syndrome Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000004098 Tetracycline Substances 0.000 description 4
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 4
- 229960000571 acetazolamide Drugs 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 4
- 229960003437 aminoglutethimide Drugs 0.000 description 4
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
- 229960003831 articaine Drugs 0.000 description 4
- 229960004099 azithromycin Drugs 0.000 description 4
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 4
- 229940125717 barbiturate Drugs 0.000 description 4
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 4
- 229940049706 benzodiazepine Drugs 0.000 description 4
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 229960000623 carbamazepine Drugs 0.000 description 4
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 4
- 230000004656 cell transport Effects 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 201000007455 central nervous system cancer Diseases 0.000 description 4
- 229960003677 chloroquine Drugs 0.000 description 4
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 4
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 4
- 229960003405 ciprofloxacin Drugs 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 229960003957 dexamethasone Drugs 0.000 description 4
- 229960001259 diclofenac Drugs 0.000 description 4
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 4
- XXEPPPIWZFICOJ-UHFFFAOYSA-N diethylpropion Chemical compound CCN(CC)C(C)C(=O)C1=CC=CC=C1 XXEPPPIWZFICOJ-UHFFFAOYSA-N 0.000 description 4
- 229960004890 diethylpropion Drugs 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 229960005426 doxepin Drugs 0.000 description 4
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 4
- 229960002472 eletriptan Drugs 0.000 description 4
- PWVXXGRKLHYWKM-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2CCS(=O)(=O)C1=CC=CC=C1 PWVXXGRKLHYWKM-LJQANCHMSA-N 0.000 description 4
- 229960003276 erythromycin Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000013613 expression plasmid Substances 0.000 description 4
- 208000030533 eye disease Diseases 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 229960002390 flurbiprofen Drugs 0.000 description 4
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 4
- 235000019152 folic acid Nutrition 0.000 description 4
- 239000011724 folic acid Substances 0.000 description 4
- 229960002870 gabapentin Drugs 0.000 description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
- CHPZKNULDCNCBW-UHFFFAOYSA-N gallium nitrate Chemical compound [Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O CHPZKNULDCNCBW-UHFFFAOYSA-N 0.000 description 4
- 229960002963 ganciclovir Drugs 0.000 description 4
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 4
- 229960003923 gatifloxacin Drugs 0.000 description 4
- 229960002518 gentamicin Drugs 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 229960000908 idarubicin Drugs 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 230000000302 ischemic effect Effects 0.000 description 4
- 229960004752 ketorolac Drugs 0.000 description 4
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 4
- 229960001848 lamotrigine Drugs 0.000 description 4
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 4
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 4
- 229960004338 leuprorelin Drugs 0.000 description 4
- 229960001977 loracarbef Drugs 0.000 description 4
- JAPHQRWPEGVNBT-UTUOFQBUSA-M loracarbef anion Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CC[C@@H]32)C([O-])=O)=O)N)=CC=CC=C1 JAPHQRWPEGVNBT-UTUOFQBUSA-M 0.000 description 4
- 229960004391 lorazepam Drugs 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 229960001924 melphalan Drugs 0.000 description 4
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 4
- 229960001428 mercaptopurine Drugs 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- 229960001703 methylphenobarbital Drugs 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 229960004927 neomycin Drugs 0.000 description 4
- 229940053128 nerve growth factor Drugs 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 201000001119 neuropathy Diseases 0.000 description 4
- 230000007823 neuropathy Effects 0.000 description 4
- 229960001180 norfloxacin Drugs 0.000 description 4
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 4
- 229960001914 paromomycin Drugs 0.000 description 4
- UOZODPSAJZTQNH-LSWIJEOBSA-N paromomycin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO UOZODPSAJZTQNH-LSWIJEOBSA-N 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229960000436 phendimetrazine Drugs 0.000 description 4
- 229960002695 phenobarbital Drugs 0.000 description 4
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 4
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229960001233 pregabalin Drugs 0.000 description 4
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 229960003981 proparacaine Drugs 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- HXCHCVDVKSCDHU-PJKCJEBCSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-(ethylamino)-4-methoxyoxan-2-yl]oxy-4-hydroxy-6-[[(2s,5z,9r,13e)-9-hydroxy-12-(methoxycarbonylamino)-13-[2-(methyltrisulfanyl)ethylidene]-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-2-m Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-PJKCJEBCSA-N 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 229960002673 sulfacetamide Drugs 0.000 description 4
- SKIVFJLNDNKQPD-UHFFFAOYSA-N sulfacetamide Chemical compound CC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 SKIVFJLNDNKQPD-UHFFFAOYSA-N 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229960002180 tetracycline Drugs 0.000 description 4
- 229930101283 tetracycline Natural products 0.000 description 4
- 235000019364 tetracycline Nutrition 0.000 description 4
- 150000003522 tetracyclines Chemical class 0.000 description 4
- 229960000337 tetryzoline Drugs 0.000 description 4
- 229960001196 thiotepa Drugs 0.000 description 4
- 229960001918 tiagabine Drugs 0.000 description 4
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 4
- 229960000707 tobramycin Drugs 0.000 description 4
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 4
- 229960004394 topiramate Drugs 0.000 description 4
- 230000031998 transcytosis Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 239000012581 transferrin Substances 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 4
- 229960001082 trimethoprim Drugs 0.000 description 4
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 4
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 4
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 4
- 229960004276 zoledronic acid Drugs 0.000 description 4
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 3
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 3
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Aminopropanesulfonate Chemical compound NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 description 3
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000011403 Alexander disease Diseases 0.000 description 3
- 108091023037 Aptamer Proteins 0.000 description 3
- 108010001478 Bacitracin Proteins 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 108010092160 Dactinomycin Proteins 0.000 description 3
- 241001269238 Data Species 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 3
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 3
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 3
- MEPSBMMZQBMKHM-UHFFFAOYSA-N Lomatiol Natural products CC(=C/CC1=C(O)C(=O)c2ccccc2C1=O)CO MEPSBMMZQBMKHM-UHFFFAOYSA-N 0.000 description 3
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 3
- 208000019022 Mood disease Diseases 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 3
- 102400000058 Neuregulin-1 Human genes 0.000 description 3
- 108090000556 Neuregulin-1 Proteins 0.000 description 3
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 3
- 206010061334 Partial seizures Diseases 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- 108010033276 Peptide Fragments Proteins 0.000 description 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 3
- 102100022036 Presenilin-2 Human genes 0.000 description 3
- 208000024777 Prion disease Diseases 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 206010058895 Psychogenic seizure Diseases 0.000 description 3
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 3
- CIEYTVIYYGTCCI-UHFFFAOYSA-N SJ000286565 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(O)C(=O)C2=C1 CIEYTVIYYGTCCI-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000005864 Sulphur Substances 0.000 description 3
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 3
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 3
- 201000006791 West syndrome Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 206010000269 abscess Diseases 0.000 description 3
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 3
- 229960003805 amantadine Drugs 0.000 description 3
- 229920002892 amber Polymers 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 3
- 229960003071 bacitracin Drugs 0.000 description 3
- 229930184125 bacitracin Natural products 0.000 description 3
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 3
- 201000008916 benign epilepsy with centrotemporal spikes Diseases 0.000 description 3
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 3
- 229960001561 bleomycin Drugs 0.000 description 3
- 210000004781 brain capillary Anatomy 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 229930195731 calicheamicin Natural products 0.000 description 3
- 150000001720 carbohydrates Chemical group 0.000 description 3
- 229960004261 cefotaxime Drugs 0.000 description 3
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 3
- 229960002682 cefoxitin Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 208000033205 childhood epilepsy with centrotemporal spikes Diseases 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 229960000684 cytarabine Drugs 0.000 description 3
- 229960000640 dactinomycin Drugs 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 3
- 229960000632 dexamfetamine Drugs 0.000 description 3
- 229960002656 didanosine Drugs 0.000 description 3
- 229960000616 diflunisal Drugs 0.000 description 3
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 3
- 229960003530 donepezil Drugs 0.000 description 3
- 229960003722 doxycycline Drugs 0.000 description 3
- FSIRXIHZBIXHKT-MHTVFEQDSA-N edatrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CC(CC)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FSIRXIHZBIXHKT-MHTVFEQDSA-N 0.000 description 3
- 229950006700 edatrexate Drugs 0.000 description 3
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 3
- 206010014599 encephalitis Diseases 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 239000002532 enzyme inhibitor Substances 0.000 description 3
- 229940125532 enzyme inhibitor Drugs 0.000 description 3
- 229960001904 epirubicin Drugs 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229960000304 folic acid Drugs 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- KNOSIOWNDGUGFJ-UHFFFAOYSA-N hydroxysesamone Natural products C1=CC(O)=C2C(=O)C(CC=C(C)C)=C(O)C(=O)C2=C1O KNOSIOWNDGUGFJ-UHFFFAOYSA-N 0.000 description 3
- 229960001101 ifosfamide Drugs 0.000 description 3
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 3
- 238000011532 immunohistochemical staining Methods 0.000 description 3
- 229960000905 indomethacin Drugs 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 206010022437 insomnia Diseases 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- SIUGQQMOYSVTAT-UHFFFAOYSA-N lapachol Natural products CC(=CCC1C(O)C(=O)c2ccccc2C1=O)C SIUGQQMOYSVTAT-UHFFFAOYSA-N 0.000 description 3
- 229960004194 lidocaine Drugs 0.000 description 3
- 210000003712 lysosome Anatomy 0.000 description 3
- 230000001868 lysosomic effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 208000005264 motor neuron disease Diseases 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 229960002009 naproxen Drugs 0.000 description 3
- CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 3
- 229940105623 neo-synephrine Drugs 0.000 description 3
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 3
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 3
- 210000003463 organelle Anatomy 0.000 description 3
- 229960001756 oxaliplatin Drugs 0.000 description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 229960002340 pentostatin Drugs 0.000 description 3
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 229960001802 phenylephrine Drugs 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 229960003111 prochlorperazine Drugs 0.000 description 3
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 3
- 229960003387 progesterone Drugs 0.000 description 3
- 239000000186 progesterone Substances 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000005180 public health Effects 0.000 description 3
- 229960004622 raloxifene Drugs 0.000 description 3
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 229960004136 rivastigmine Drugs 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 208000019116 sleep disease Diseases 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 229960001685 tacrine Drugs 0.000 description 3
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 3
- 229960001603 tamoxifen Drugs 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 229960000604 valproic acid Drugs 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 229950009268 zinostatin Drugs 0.000 description 3
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 description 2
- NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 description 2
- WYDUSKDSKCASEF-LJQANCHMSA-N (1s)-1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol Chemical compound C([C@](O)(C1CCCCC1)C=1C=CC=CC=1)CN1CCCC1 WYDUSKDSKCASEF-LJQANCHMSA-N 0.000 description 2
- WDQLRUYAYXDIFW-RWKIJVEZSA-N (2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-4-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol Chemical compound O[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O1 WDQLRUYAYXDIFW-RWKIJVEZSA-N 0.000 description 2
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 2
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 2
- CGMTUJFWROPELF-YPAAEMCBSA-N (3E,5S)-5-[(2S)-butan-2-yl]-3-(1-hydroxyethylidene)pyrrolidine-2,4-dione Chemical compound CC[C@H](C)[C@@H]1NC(=O)\C(=C(/C)O)C1=O CGMTUJFWROPELF-YPAAEMCBSA-N 0.000 description 2
- OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 2
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 2
- GUXHBMASAHGULD-SEYHBJAFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O GUXHBMASAHGULD-SEYHBJAFSA-N 0.000 description 2
- ALARQZQTBTVLJV-CYBMUJFWSA-N (5r)-5-ethyl-1-methyl-5-phenyl-1,3-diazinane-2,4,6-trione Chemical compound C=1C=CC=CC=1[C@]1(CC)C(=O)NC(=O)N(C)C1=O ALARQZQTBTVLJV-CYBMUJFWSA-N 0.000 description 2
- XRBSKUSTLXISAB-XVVDYKMHSA-N (5r,6r,7r,8r)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydrobenzo[f][1,3]benzodioxole-6-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H](CO)[C@@H]2C(O)=O)=C1 XRBSKUSTLXISAB-XVVDYKMHSA-N 0.000 description 2
- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 description 2
- JXVAMODRWBNUSF-KZQKBALLSA-N (7s,9r,10r)-7-[(2r,4s,5s,6s)-5-[[(2s,4as,5as,7s,9s,9ar,10ar)-2,9-dimethyl-3-oxo-4,4a,5a,6,7,9,9a,10a-octahydrodipyrano[4,2-a:4',3'-e][1,4]dioxin-7-yl]oxy]-4-(dimethylamino)-6-methyloxan-2-yl]oxy-10-[(2s,4s,5s,6s)-4-(dimethylamino)-5-hydroxy-6-methyloxan-2 Chemical compound O([C@@H]1C2=C(O)C=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C2[C@@H](O[C@@H]2O[C@@H](C)[C@@H](O[C@@H]3O[C@@H](C)[C@H]4O[C@@H]5O[C@@H](C)C(=O)C[C@@H]5O[C@H]4C3)[C@H](C2)N(C)C)C[C@]1(O)CC)[C@H]1C[C@H](N(C)C)[C@H](O)[C@H](C)O1 JXVAMODRWBNUSF-KZQKBALLSA-N 0.000 description 2
- INAUWOVKEZHHDM-PEDBPRJASA-N (7s,9s)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1 INAUWOVKEZHHDM-PEDBPRJASA-N 0.000 description 2
- RCFNNLSZHVHCEK-IMHLAKCZSA-N (7s,9s)-7-(4-amino-6-methyloxan-2-yl)oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound [Cl-].O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)C1CC([NH3+])CC(C)O1 RCFNNLSZHVHCEK-IMHLAKCZSA-N 0.000 description 2
- IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 description 2
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 description 2
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 2
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 2
- XFDJYSQDBULQSI-QFIPXVFZSA-N (R)-doxapram Chemical compound C([C@H]1CN(C(C1(C=1C=CC=CC=1)C=1C=CC=CC=1)=O)CC)CN1CCOCC1 XFDJYSQDBULQSI-QFIPXVFZSA-N 0.000 description 2
- QKDHBVNJCZBTMR-LLVKDONJSA-N (R)-temafloxacin Chemical compound C1CN[C@H](C)CN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1=CC=C(F)C=C1F QKDHBVNJCZBTMR-LLVKDONJSA-N 0.000 description 2
- VSWBSWWIRNCQIJ-GJZGRUSLSA-N (R,R)-asenapine Chemical compound O1C2=CC=CC=C2[C@@H]2CN(C)C[C@H]2C2=CC(Cl)=CC=C21 VSWBSWWIRNCQIJ-GJZGRUSLSA-N 0.000 description 2
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 2
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 2
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 description 2
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 2
- AGNGYMCLFWQVGX-AGFFZDDWSA-N (e)-1-[(2s)-2-amino-2-carboxyethoxy]-2-diazonioethenolate Chemical compound OC(=O)[C@@H](N)CO\C([O-])=C\[N+]#N AGNGYMCLFWQVGX-AGFFZDDWSA-N 0.000 description 2
- ZEHYJZXQEQOSON-AATRIKPKSA-N (e)-1-chloro-3-ethylpent-1-en-4-yn-3-ol Chemical compound CCC(O)(C#C)\C=C\Cl ZEHYJZXQEQOSON-AATRIKPKSA-N 0.000 description 2
- FONKWHRXTPJODV-DNQXCXABSA-N 1,3-bis[2-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydro-3h-pyrrolo[3,2-e]indole-6-carbonyl]-1h-indol-5-yl]urea Chemical compound C1([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C4=CC(O)=C5NC=C(C5=C4[C@H](CCl)C3)C)=C2C=C(O)C2=C1C(C)=CN2 FONKWHRXTPJODV-DNQXCXABSA-N 0.000 description 2
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 2
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 description 2
- BOMZMNZEXMAQQW-UHFFFAOYSA-N 2,5,11-trimethyl-6h-pyrido[4,3-b]carbazol-2-ium-9-ol;acetate Chemical compound CC([O-])=O.C[N+]1=CC=C2C(C)=C(NC=3C4=CC(O)=CC=3)C4=C(C)C2=C1 BOMZMNZEXMAQQW-UHFFFAOYSA-N 0.000 description 2
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 2
- QCXJFISCRQIYID-IAEPZHFASA-N 2-amino-1-n-[(3s,6s,7r,10s,16s)-3-[(2s)-butan-2-yl]-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-10-propan-2-yl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-4,6-dimethyl-3-oxo-9-n-[(3s,6s,7r,10s,16s)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propa Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N=C2C(C(=O)N[C@@H]3C(=O)N[C@H](C(N4CCC[C@H]4C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]3C)=O)[C@@H](C)CC)=C(N)C(=O)C(C)=C2O2)C2=C(C)C=C1 QCXJFISCRQIYID-IAEPZHFASA-N 0.000 description 2
- VNBAOSVONFJBKP-UHFFFAOYSA-N 2-chloro-n,n-bis(2-chloroethyl)propan-1-amine;hydrochloride Chemical compound Cl.CC(Cl)CN(CCCl)CCCl VNBAOSVONFJBKP-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- YIMDLWDNDGKDTJ-QLKYHASDSA-N 3'-deamino-3'-(3-cyanomorpholin-4-yl)doxorubicin Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1C#N YIMDLWDNDGKDTJ-QLKYHASDSA-N 0.000 description 2
- PWMYMKOUNYTVQN-UHFFFAOYSA-N 3-(8,8-diethyl-2-aza-8-germaspiro[4.5]decan-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1C[Ge](CC)(CC)CCC11CN(CCCN(C)C)CC1 PWMYMKOUNYTVQN-UHFFFAOYSA-N 0.000 description 2
- QGJZLNKBHJESQX-UHFFFAOYSA-N 3-Epi-Betulin-Saeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(=C)C)C5C4CCC3C21C QGJZLNKBHJESQX-UHFFFAOYSA-N 0.000 description 2
- PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 description 2
- CLOUCVRNYSHRCF-UHFFFAOYSA-N 3beta-Hydroxy-20(29)-Lupen-3,27-oic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C(O)=O)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C CLOUCVRNYSHRCF-UHFFFAOYSA-N 0.000 description 2
- CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 2
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 2
- HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 description 2
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 2
- GJOHLWZHWQUKAU-UHFFFAOYSA-N 5-azaniumylpentan-2-yl-(6-methoxyquinolin-8-yl)azanium;dihydrogen phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 GJOHLWZHWQUKAU-UHFFFAOYSA-N 0.000 description 2
- XKFPYPQQHFEXRZ-UHFFFAOYSA-N 5-methyl-N'-(phenylmethyl)-3-isoxazolecarbohydrazide Chemical compound O1C(C)=CC(C(=O)NNCC=2C=CC=CC=2)=N1 XKFPYPQQHFEXRZ-UHFFFAOYSA-N 0.000 description 2
- LCGTWRLJTMHIQZ-UHFFFAOYSA-N 5H-dibenzo[b,f]azepine Chemical compound C1=CC2=CC=CC=C2NC2=CC=CC=C21 LCGTWRLJTMHIQZ-UHFFFAOYSA-N 0.000 description 2
- HGGAKXAHAYOLDJ-FHZUQPTBSA-N 6alpha-[(R)-1-hydroxyethyl]-2-[(R)-tetrahydrofuran-2-yl]pen-2-em-3-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)[C@H](O)C)C=1[C@H]1CCCO1 HGGAKXAHAYOLDJ-FHZUQPTBSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 2
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 description 2
- HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 2
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 2
- 206010000117 Abnormal behaviour Diseases 0.000 description 2
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 2
- 208000008811 Agoraphobia Diseases 0.000 description 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 2
- FDQGNLOWMMVRQL-UHFFFAOYSA-N Allobarbital Chemical compound C=CCC1(CC=C)C(=O)NC(=O)NC1=O FDQGNLOWMMVRQL-UHFFFAOYSA-N 0.000 description 2
- WKEMJKQOLOHJLZ-UHFFFAOYSA-N Almogran Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CS(=O)(=O)N1CCCC1 WKEMJKQOLOHJLZ-UHFFFAOYSA-N 0.000 description 2
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 2
- CEIZFXOZIQNICU-UHFFFAOYSA-N Alternaria alternata Crofton-weed toxin Natural products CCC(C)C1NC(=O)C(C(C)=O)=C1O CEIZFXOZIQNICU-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OVCDSSHSILBFBN-UHFFFAOYSA-N Amodiaquine Chemical compound C1=C(O)C(CN(CC)CC)=CC(NC=2C3=CC=C(Cl)C=C3N=CC=2)=C1 OVCDSSHSILBFBN-UHFFFAOYSA-N 0.000 description 2
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 2
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- CJLHTKGWEUGORV-UHFFFAOYSA-N Artemin Chemical compound C1CC2(C)C(O)CCC(=C)C2(O)C2C1C(C)C(=O)O2 CJLHTKGWEUGORV-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 108700023155 Aspartoacylases Proteins 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- 241000228245 Aspergillus niger Species 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 2
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 2
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- 206010003805 Autism Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 206010049612 Autonomic seizure Diseases 0.000 description 2
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 2
- 239000005465 B01AC22 - Prasugrel Substances 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 206010070530 Benign rolandic epilepsy Diseases 0.000 description 2
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 2
- 102100021257 Beta-secretase 1 Human genes 0.000 description 2
- 101710150192 Beta-secretase 1 Proteins 0.000 description 2
- DIZWSDNSTNAYHK-XGWVBXMLSA-N Betulinic acid Natural products CC(=C)[C@@H]1C[C@H]([C@H]2CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(=O)O DIZWSDNSTNAYHK-XGWVBXMLSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- 206010006542 Bulbar palsy Diseases 0.000 description 2
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 2
- MBABCNBNDNGODA-LTGLSHGVSA-N Bullatacin Natural products O=C1C(C[C@H](O)CCCCCCCCCC[C@@H](O)[C@@H]2O[C@@H]([C@@H]3O[C@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 MBABCNBNDNGODA-LTGLSHGVSA-N 0.000 description 2
- KGGVWMAPBXIMEM-ZRTAFWODSA-N Bullatacinone Chemical compound O1[C@@H]([C@@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCC[C@H]2OC(=O)[C@H](CC(C)=O)C2)CC1 KGGVWMAPBXIMEM-ZRTAFWODSA-N 0.000 description 2
- KGGVWMAPBXIMEM-JQFCFGFHSA-N Bullatacinone Natural products O=C(C[C@H]1C(=O)O[C@H](CCCCCCCCCC[C@H](O)[C@@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)C1)C KGGVWMAPBXIMEM-JQFCFGFHSA-N 0.000 description 2
- 108010037003 Buserelin Proteins 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 102000003846 Carbonic anhydrases Human genes 0.000 description 2
- 108090000209 Carbonic anhydrases Proteins 0.000 description 2
- SHHKQEUPHAENFK-UHFFFAOYSA-N Carboquone Chemical compound O=C1C(C)=C(N2CC2)C(=O)C(C(COC(N)=O)OC)=C1N1CC1 SHHKQEUPHAENFK-UHFFFAOYSA-N 0.000 description 2
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 2
- XCDXSSFOJZZGQC-UHFFFAOYSA-N Chlornaphazine Chemical compound C1=CC=CC2=CC(N(CCCl)CCCl)=CC=C21 XCDXSSFOJZZGQC-UHFFFAOYSA-N 0.000 description 2
- MKQWTWSXVILIKJ-LXGUWJNJSA-N Chlorozotocin Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)NC(=O)N(N=O)CCCl MKQWTWSXVILIKJ-LXGUWJNJSA-N 0.000 description 2
- UDKCHVLMFQVBAA-UHFFFAOYSA-M Choline salicylate Chemical compound C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O UDKCHVLMFQVBAA-UHFFFAOYSA-M 0.000 description 2
- 201000005262 Chondroma Diseases 0.000 description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 description 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 2
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 2
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 2
- 208000010200 Cockayne syndrome Diseases 0.000 description 2
- 108010078777 Colistin Proteins 0.000 description 2
- 208000033001 Complex partial seizures Diseases 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
- 201000007336 Cryptococcosis Diseases 0.000 description 2
- 241000221204 Cryptococcus neoformans Species 0.000 description 2
- 229930188224 Cryptophycin Natural products 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 2
- 208000024254 Delusional disease Diseases 0.000 description 2
- NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 description 2
- FMTDIUIBLCQGJB-UHFFFAOYSA-N Demethylchlortetracyclin Natural products C1C2C(O)C3=C(Cl)C=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O FMTDIUIBLCQGJB-UHFFFAOYSA-N 0.000 description 2
- 108010002156 Depsipeptides Proteins 0.000 description 2
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 2
- AUGQEEXBDZWUJY-ZLJUKNTDSA-N Diacetoxyscirpenol Chemical compound C([C@]12[C@]3(C)[C@H](OC(C)=O)[C@@H](O)[C@H]1O[C@@H]1C=C(C)CC[C@@]13COC(=O)C)O2 AUGQEEXBDZWUJY-ZLJUKNTDSA-N 0.000 description 2
- WYQPLTPSGFELIB-JTQPXKBDSA-N Difluprednate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2CC[C@@](C(=O)COC(C)=O)(OC(=O)CCC)[C@@]2(C)C[C@@H]1O WYQPLTPSGFELIB-JTQPXKBDSA-N 0.000 description 2
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 2
- CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 description 2
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 2
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 2
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 description 2
- 102400001368 Epidermal growth factor Human genes 0.000 description 2
- OBMLHUPNRURLOK-XGRAFVIBSA-N Epitiostanol Chemical compound C1[C@@H]2S[C@@H]2C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OBMLHUPNRURLOK-XGRAFVIBSA-N 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- VTUSIVBDOCDNHS-UHFFFAOYSA-N Etidocaine Chemical compound CCCN(CC)C(CC)C(=O)NC1=C(C)C=CC=C1C VTUSIVBDOCDNHS-UHFFFAOYSA-N 0.000 description 2
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 2
- 208000024720 Fabry Disease Diseases 0.000 description 2
- 208000001948 Farber Lipogranulomatosis Diseases 0.000 description 2
- 208000002091 Febrile Seizures Diseases 0.000 description 2
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 2
- XWLUWCNOOVRFPX-UHFFFAOYSA-N Fosphenytoin Chemical compound O=C1N(COP(O)(=O)O)C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 XWLUWCNOOVRFPX-UHFFFAOYSA-N 0.000 description 2
- 208000024412 Friedreich ataxia Diseases 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 201000008892 GM1 Gangliosidosis Diseases 0.000 description 2
- 201000004066 Ganglioglioma Diseases 0.000 description 2
- 208000015872 Gaucher disease Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 2
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- 108010069236 Goserelin Proteins 0.000 description 2
- 108010026389 Gramicidin Proteins 0.000 description 2
- AIJTTZAVMXIJGM-UHFFFAOYSA-N Grepafloxacin Chemical compound C1CNC(C)CN1C(C(=C1C)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 AIJTTZAVMXIJGM-UHFFFAOYSA-N 0.000 description 2
- 244000041633 Grewia tenax Species 0.000 description 2
- 235000005612 Grewia tenax Nutrition 0.000 description 2
- FOHHNHSLJDZUGQ-VWLOTQADSA-N Halofantrine Chemical compound FC(F)(F)C1=CC=C2C([C@@H](O)CCN(CCCC)CCCC)=CC3=C(Cl)C=C(Cl)C=C3C2=C1 FOHHNHSLJDZUGQ-VWLOTQADSA-N 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 2
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 2
- 208000035899 Infantile spasms syndrome Diseases 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- JUZNIMUFDBIJCM-ANEDZVCMSA-N Invanz Chemical compound O=C([C@H]1NC[C@H](C1)SC=1[C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)NC1=CC=CC(C(O)=O)=C1 JUZNIMUFDBIJCM-ANEDZVCMSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 2
- 208000027747 Kennedy disease Diseases 0.000 description 2
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 2
- 208000028226 Krabbe disease Diseases 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- 229920001491 Lentinan Polymers 0.000 description 2
- 208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 2
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- TYMRLRRVMHJFTF-UHFFFAOYSA-N Mafenide Chemical compound NCC1=CC=C(S(N)(=O)=O)C=C1 TYMRLRRVMHJFTF-UHFFFAOYSA-N 0.000 description 2
- MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- VJRAUFKOOPNFIQ-UHFFFAOYSA-N Marcellomycin Natural products C12=C(O)C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C=C2C(C(=O)OC)C(CC)(O)CC1OC(OC1C)CC(N(C)C)C1OC(OC1C)CC(O)C1OC1CC(O)C(O)C(C)O1 VJRAUFKOOPNFIQ-UHFFFAOYSA-N 0.000 description 2
- 229930126263 Maytansine Natural products 0.000 description 2
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 2
- GZENKSODFLBBHQ-ILSZZQPISA-N Medrysone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@H](C(C)=O)CC[C@H]21 GZENKSODFLBBHQ-ILSZZQPISA-N 0.000 description 2
- 208000000172 Medulloblastoma Diseases 0.000 description 2
- JCYZMTMYPZHVBF-UHFFFAOYSA-N Melarsoprol Chemical compound NC1=NC(N)=NC(NC=2C=CC(=CC=2)[As]2SC(CO)CS2)=N1 JCYZMTMYPZHVBF-UHFFFAOYSA-N 0.000 description 2
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 2
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 2
- 206010027294 Menkes' syndrome Diseases 0.000 description 2
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 2
- IVDYZAAPOLNZKG-KWHRADDSSA-N Mepitiostane Chemical compound O([C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)C[C@H]5S[C@H]5C[C@@H]4CC[C@H]3[C@@H]2CC1)C)C1(OC)CCCC1 IVDYZAAPOLNZKG-KWHRADDSSA-N 0.000 description 2
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 2
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 2
- FWJKNZONDWOGMI-UHFFFAOYSA-N Metharbital Chemical compound CCC1(CC)C(=O)NC(=O)N(C)C1=O FWJKNZONDWOGMI-UHFFFAOYSA-N 0.000 description 2
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 2
- KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- YLXDSYKOBKBWJQ-LBPRGKRZSA-N N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e]benzofuran-8-yl]ethyl]propanamide Chemical compound C1=C2OCCC2=C2[C@H](CCNC(=O)CC)CCC2=C1 YLXDSYKOBKBWJQ-LBPRGKRZSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 102000005348 Neuraminidase Human genes 0.000 description 2
- 108010006232 Neuraminidase Proteins 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 108090000099 Neurotrophin-4 Proteins 0.000 description 2
- 241000208125 Nicotiana Species 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 208000014060 Niemann-Pick disease Diseases 0.000 description 2
- SYNHCENRCUAUNM-UHFFFAOYSA-N Nitrogen mustard N-oxide hydrochloride Chemical compound Cl.ClCC[N+]([O-])(C)CCCl SYNHCENRCUAUNM-UHFFFAOYSA-N 0.000 description 2
- KGTDRFCXGRULNK-UHFFFAOYSA-N Nogalamycin Natural products COC1C(OC)(C)C(OC)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=C4C5(C)OC(C(C(C5O)N(C)C)O)OC4=C3C3=O)=C3C=C2C(C(=O)OC)C(C)(O)C1 KGTDRFCXGRULNK-UHFFFAOYSA-N 0.000 description 2
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 2
- 201000010133 Oligodendroglioma Diseases 0.000 description 2
- 229930187135 Olivomycin Natural products 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 2
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 244000131316 Panax pseudoginseng Species 0.000 description 2
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 2
- 235000003140 Panax quinquefolius Nutrition 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- VQASKUSHBVDKGU-UHFFFAOYSA-N Paramethadione Chemical compound CCC1(C)OC(=O)N(C)C1=O VQASKUSHBVDKGU-UHFFFAOYSA-N 0.000 description 2
- 208000006199 Parasomnias Diseases 0.000 description 2
- 208000037158 Partial Epilepsies Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108010057150 Peplomycin Proteins 0.000 description 2
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 2
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 2
- AJOQSQHYDOFIOX-UHFFFAOYSA-N Pheneturide Chemical compound NC(=O)NC(=O)C(CC)C1=CC=CC=C1 AJOQSQHYDOFIOX-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
- 208000024571 Pick disease Diseases 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- YQKAVWCGQQXBGW-UHFFFAOYSA-N Piperocaine Chemical compound CC1CCCCN1CCCOC(=O)C1=CC=CC=C1 YQKAVWCGQQXBGW-UHFFFAOYSA-N 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010093965 Polymyxin B Proteins 0.000 description 2
- 208000010366 Postpoliomyelitis syndrome Diseases 0.000 description 2
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 2
- HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 2
- 102000015499 Presenilins Human genes 0.000 description 2
- 108010050254 Presenilins Proteins 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- CAJIGINSTLKQMM-UHFFFAOYSA-N Propoxycaine Chemical compound CCCOC1=CC(N)=CC=C1C(=O)OCCN(CC)CC CAJIGINSTLKQMM-UHFFFAOYSA-N 0.000 description 2
- 101710150593 Protein beta Proteins 0.000 description 2
- AQXXZDYPVDOQEE-MXDQRGINSA-N Pyrantel pamoate Chemical compound CN1CCCN=C1\C=C\C1=CC=CS1.C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 AQXXZDYPVDOQEE-MXDQRGINSA-N 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 208000005587 Refsum Disease Diseases 0.000 description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 2
- 208000004974 Rolandic Epilepsy Diseases 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 206010040703 Simple partial seizures Diseases 0.000 description 2
- 229920000519 Sizofiran Polymers 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 102000005262 Sulfatase Human genes 0.000 description 2
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 2
- 208000022292 Tay-Sachs disease Diseases 0.000 description 2
- 108010053950 Teicoplanin Proteins 0.000 description 2
- 108010039185 Tenecteplase Proteins 0.000 description 2
- CGMTUJFWROPELF-UHFFFAOYSA-N Tenuazonic acid Natural products CCC(C)C1NC(=O)C(=C(C)/O)C1=O CGMTUJFWROPELF-UHFFFAOYSA-N 0.000 description 2
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 2
- GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 description 2
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 2
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 description 2
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 206010043994 Tonic convulsion Diseases 0.000 description 2
- 101710183280 Topoisomerase Proteins 0.000 description 2
- 208000035317 Total hypoxanthine-guanine phosphoribosyl transferase deficiency Diseases 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 102100031013 Transgelin Human genes 0.000 description 2
- SHGAZHPCJJPHSC-NWVFGJFESA-N Tretinoin Chemical compound OC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NWVFGJFESA-N 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- UMILHIMHKXVDGH-UHFFFAOYSA-N Triethylene glycol diglycidyl ether Chemical compound C1OC1COCCOCCOCCOCC1CO1 UMILHIMHKXVDGH-UHFFFAOYSA-N 0.000 description 2
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 description 2
- WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical compound N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 description 2
- 108010059993 Vancomycin Proteins 0.000 description 2
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 208000014070 Vestibular schwannoma Diseases 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 229940122803 Vinca alkaloid Drugs 0.000 description 2
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 2
- IHGLINDYFMDHJG-UHFFFAOYSA-N [2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCC1 IHGLINDYFMDHJG-UHFFFAOYSA-N 0.000 description 2
- XZSRRNFBEIOBDA-CFNBKWCHSA-N [2-[(2s,4s)-4-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1h-tetracen-2-yl]-2-oxoethyl] 2,2-diethoxyacetate Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)C(OCC)OCC)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 XZSRRNFBEIOBDA-CFNBKWCHSA-N 0.000 description 2
- 229960004748 abacavir Drugs 0.000 description 2
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 2
- 208000028311 absence seizure Diseases 0.000 description 2
- ZOZKYEHVNDEUCO-XUTVFYLZSA-N aceglatone Chemical compound O1C(=O)[C@H](OC(C)=O)[C@@H]2OC(=O)[C@@H](OC(=O)C)[C@@H]21 ZOZKYEHVNDEUCO-XUTVFYLZSA-N 0.000 description 2
- 229950002684 aceglatone Drugs 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- YQNQNVDNTFHQSW-UHFFFAOYSA-N acetic acid [2-[[(5-nitro-2-thiazolyl)amino]-oxomethyl]phenyl] ester Chemical compound CC(=O)OC1=CC=CC=C1C(=O)NC1=NC=C([N+]([O-])=O)S1 YQNQNVDNTFHQSW-UHFFFAOYSA-N 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 2
- 208000004064 acoustic neuroma Diseases 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 2
- 229950004955 adozelesin Drugs 0.000 description 2
- BYRVKDUQDLJUBX-JJCDCTGGSA-N adozelesin Chemical compound C1=CC=C2OC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)NC=C5C)=CC2=C1 BYRVKDUQDLJUBX-JJCDCTGGSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 208000030597 adult Refsum disease Diseases 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 229960002669 albendazole Drugs 0.000 description 2
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229940062527 alendronate Drugs 0.000 description 2
- 229960000880 allobarbital Drugs 0.000 description 2
- 229960002133 almotriptan Drugs 0.000 description 2
- 229960004538 alprazolam Drugs 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 229960003318 alteplase Drugs 0.000 description 2
- 229960004821 amikacin Drugs 0.000 description 2
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229960003896 aminopterin Drugs 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 229960001444 amodiaquine Drugs 0.000 description 2
- 229960002519 amoxapine Drugs 0.000 description 2
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 2
- 229960003022 amoxicillin Drugs 0.000 description 2
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 2
- 229940025084 amphetamine Drugs 0.000 description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
- 229960003942 amphotericin b Drugs 0.000 description 2
- 229960001220 amsacrine Drugs 0.000 description 2
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 2
- BBDAGFIXKZCXAH-CCXZUQQUSA-N ancitabine Chemical compound N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 BBDAGFIXKZCXAH-CCXZUQQUSA-N 0.000 description 2
- 229950000242 ancitabine Drugs 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000000561 anti-psychotic effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 229960004046 apomorphine Drugs 0.000 description 2
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
- 229960003153 aprobarbital Drugs 0.000 description 2
- UORJNBVJVRLXMQ-UHFFFAOYSA-N aprobarbital Chemical compound C=CCC1(C(C)C)C(=O)NC(=O)NC1=O UORJNBVJVRLXMQ-UHFFFAOYSA-N 0.000 description 2
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 description 2
- 229960005245 asenapine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 102000018919 aspartoacylase Human genes 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229960003277 atazanavir Drugs 0.000 description 2
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 2
- 229960002430 atomoxetine Drugs 0.000 description 2
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 229960003159 atovaquone Drugs 0.000 description 2
- KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 description 2
- 229940120638 avastin Drugs 0.000 description 2
- 229960002756 azacitidine Drugs 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 229950011321 azaserine Drugs 0.000 description 2
- 229960004574 azelastine Drugs 0.000 description 2
- 229960003623 azlocillin Drugs 0.000 description 2
- JTWOMNBEOCYFNV-NFFDBFGFSA-N azlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCNC1=O JTWOMNBEOCYFNV-NFFDBFGFSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 229960002699 bacampicillin Drugs 0.000 description 2
- PFOLLRNADZZWEX-FFGRCDKISA-N bacampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OC(C)OC(=O)OCC)=CC=CC=C1 PFOLLRNADZZWEX-FFGRCDKISA-N 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- 229960002319 barbital Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- GIJXKZJWITVLHI-PMOLBWCYSA-N benzatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-PMOLBWCYSA-N 0.000 description 2
- 229960001081 benzatropine Drugs 0.000 description 2
- YXKTVDFXDRQTKV-HNNXBMFYSA-N benzphetamine Chemical compound C([C@H](C)N(C)CC=1C=CC=CC=1)C1=CC=CC=C1 YXKTVDFXDRQTKV-HNNXBMFYSA-N 0.000 description 2
- 229960002837 benzphetamine Drugs 0.000 description 2
- YWGDOWXRIALTES-NRFANRHFSA-N bepotastine Chemical compound C1CN(CCCC(=O)O)CCC1O[C@H](C=1N=CC=CC=1)C1=CC=C(Cl)C=C1 YWGDOWXRIALTES-NRFANRHFSA-N 0.000 description 2
- 229960002071 bepotastine Drugs 0.000 description 2
- 229960004024 besifloxacin Drugs 0.000 description 2
- QFFGVLORLPOAEC-SNVBAGLBSA-N besifloxacin Chemical compound C1[C@H](N)CCCCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1Cl QFFGVLORLPOAEC-SNVBAGLBSA-N 0.000 description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- QZPQTZZNNJUOLS-UHFFFAOYSA-N beta-lapachone Chemical compound C12=CC=CC=C2C(=O)C(=O)C2=C1OC(C)(C)CC2 QZPQTZZNNJUOLS-UHFFFAOYSA-N 0.000 description 2
- 229960004324 betaxolol Drugs 0.000 description 2
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 2
- QGJZLNKBHJESQX-FZFNOLFKSA-N betulinic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C QGJZLNKBHJESQX-FZFNOLFKSA-N 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 229960000997 bicalutamide Drugs 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 229960002470 bimatoprost Drugs 0.000 description 2
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 description 2
- 229960003003 biperiden Drugs 0.000 description 2
- YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 description 2
- 229950008548 bisantrene Drugs 0.000 description 2
- 229950006844 bizelesin Drugs 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 2
- DYODAJAEQDVYFX-UHFFFAOYSA-N brallobarbital Chemical compound BrC(=C)CC1(CC=C)C(=O)NC(=O)NC1=O DYODAJAEQDVYFX-UHFFFAOYSA-N 0.000 description 2
- 229950002261 brallobarbital Drugs 0.000 description 2
- 229960003679 brimonidine Drugs 0.000 description 2
- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 2
- 229960000722 brinzolamide Drugs 0.000 description 2
- 229960003655 bromfenac Drugs 0.000 description 2
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 description 2
- 229960002802 bromocriptine Drugs 0.000 description 2
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 2
- 229960005520 bryostatin Drugs 0.000 description 2
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 2
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 2
- MBABCNBNDNGODA-LUVUIASKSA-N bullatacin Chemical compound O1[C@@H]([C@@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCC[C@@H](O)CC=2C(O[C@@H](C)C=2)=O)CC1 MBABCNBNDNGODA-LUVUIASKSA-N 0.000 description 2
- 229960003150 bupivacaine Drugs 0.000 description 2
- 229960001058 bupropion Drugs 0.000 description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 2
- 229960002495 buspirone Drugs 0.000 description 2
- 229960002092 busulfan Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 108700002839 cactinomycin Proteins 0.000 description 2
- 229950009908 cactinomycin Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- IVFYLRMMHVYGJH-PVPPCFLZSA-N calusterone Chemical compound C1C[C@]2(C)[C@](O)(C)CC[C@H]2[C@@H]2[C@@H](C)CC3=CC(=O)CC[C@]3(C)[C@H]21 IVFYLRMMHVYGJH-PVPPCFLZSA-N 0.000 description 2
- 229950009823 calusterone Drugs 0.000 description 2
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 2
- 238000013368 capillary electrophoresis sodium dodecyl sulfate analysis Methods 0.000 description 2
- JSVCEVCSANKFDY-SFYZADRCSA-N carbacephem Chemical compound C1CC(C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)C)[C@H]21 JSVCEVCSANKFDY-SFYZADRCSA-N 0.000 description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
- 229960004484 carbachol Drugs 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 2
- 229960003669 carbenicillin Drugs 0.000 description 2
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
- 229960004205 carbidopa Drugs 0.000 description 2
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 229960002115 carboquone Drugs 0.000 description 2
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 2
- 229930188550 carminomycin Natural products 0.000 description 2
- XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 2
- 229960003261 carmofur Drugs 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- 229960001222 carteolol Drugs 0.000 description 2
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 2
- 229950001725 carubicin Drugs 0.000 description 2
- BBZDXMBRAFTCAA-AREMUKBSSA-N carzelesin Chemical compound C1=2NC=C(C)C=2C([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)C3=CC4=CC=C(C=C4O3)N(CC)CC)=C2C=C1OC(=O)NC1=CC=CC=C1 BBZDXMBRAFTCAA-AREMUKBSSA-N 0.000 description 2
- 229950007509 carzelesin Drugs 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 229960004841 cefadroxil Drugs 0.000 description 2
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 2
- 229960003012 cefamandole Drugs 0.000 description 2
- OLVCFLKTBJRLHI-AXAPSJFSSA-N cefamandole Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](O)C=3C=CC=CC=3)[C@H]2SC1 OLVCFLKTBJRLHI-AXAPSJFSSA-N 0.000 description 2
- 229960001139 cefazolin Drugs 0.000 description 2
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 2
- 229960005495 cefotetan Drugs 0.000 description 2
- SRZNHPXWXCNNDU-RHBCBLIFSA-N cefotetan Chemical compound N([C@]1(OC)C(N2C(=C(CSC=3N(N=NN=3)C)CS[C@@H]21)C(O)=O)=O)C(=O)C1SC(=C(C(N)=O)C(O)=O)S1 SRZNHPXWXCNNDU-RHBCBLIFSA-N 0.000 description 2
- 229960002580 cefprozil Drugs 0.000 description 2
- 229960002588 cefradine Drugs 0.000 description 2
- 229960004755 ceftriaxone Drugs 0.000 description 2
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 description 2
- 229960000590 celecoxib Drugs 0.000 description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 229940106164 cephalexin Drugs 0.000 description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 229960005110 cerivastatin Drugs 0.000 description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- JQXXHWHPUNPDRT-BQVAUQFYSA-N chembl1523493 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2C=NN1CCN(C)CC1 JQXXHWHPUNPDRT-BQVAUQFYSA-N 0.000 description 2
- DDTDNCYHLGRFBM-YZEKDTGTSA-N chembl2367892 Chemical compound CC(=O)N[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1O[C@@H]([C@H]1C(N[C@@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(O)C=C(C=4)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@H](CC=4C=C(Cl)C(O5)=CC=4)C(=O)N3)C(=O)N1)C(O)=O)=O)C(C=C1Cl)=CC=C1OC1=C(O[C@H]3[C@H]([C@@H](O)[C@H](O)[C@H](CO)O3)NC(C)=O)C5=CC2=C1 DDTDNCYHLGRFBM-YZEKDTGTSA-N 0.000 description 2
- 238000002038 chemiluminescence detection Methods 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 229960005091 chloramphenicol Drugs 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- 229950008249 chlornaphazine Drugs 0.000 description 2
- 229960001480 chlorozotocin Drugs 0.000 description 2
- 229960002688 choline salicylate Drugs 0.000 description 2
- 208000017580 chronic wasting disease Diseases 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 229960001747 cinchocaine Drugs 0.000 description 2
- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- 229960001653 citalopram Drugs 0.000 description 2
- 229960002626 clarithromycin Drugs 0.000 description 2
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 2
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 2
- 229960003324 clavulanic acid Drugs 0.000 description 2
- 229960002227 clindamycin Drugs 0.000 description 2
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 2
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 2
- 229960002286 clodronic acid Drugs 0.000 description 2
- 229960004606 clomipramine Drugs 0.000 description 2
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
- 229960003009 clopidogrel Drugs 0.000 description 2
- 229960003326 cloxacillin Drugs 0.000 description 2
- LQOLIRLGBULYKD-JKIFEVAISA-N cloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-JKIFEVAISA-N 0.000 description 2
- 229960004170 clozapine Drugs 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 229960003920 cocaine Drugs 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 229960003346 colistin Drugs 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- YLRNESBGEGGQBK-UHFFFAOYSA-N cyclomethycaine Chemical compound CC1CCCCN1CCCOC(=O)C(C=C1)=CC=C1OC1CCCCC1 YLRNESBGEGGQBK-UHFFFAOYSA-N 0.000 description 2
- 229960004741 cyclomethycaine Drugs 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 229960003901 dacarbazine Drugs 0.000 description 2
- CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 229960005319 delavirdine Drugs 0.000 description 2
- 229960003715 demecarium bromide Drugs 0.000 description 2
- YHKBUDZECQDYBR-UHFFFAOYSA-L demecarium bromide Chemical compound [Br-].[Br-].C=1C=CC([N+](C)(C)C)=CC=1OC(=O)N(C)CCCCCCCCCCN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 YHKBUDZECQDYBR-UHFFFAOYSA-L 0.000 description 2
- 229960002398 demeclocycline Drugs 0.000 description 2
- 229960005052 demecolcine Drugs 0.000 description 2
- 229960003914 desipramine Drugs 0.000 description 2
- 229950003913 detorubicin Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960001042 dexmethylphenidate Drugs 0.000 description 2
- DUGOZIWVEXMGBE-CHWSQXEVSA-N dexmethylphenidate Chemical compound C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-CHWSQXEVSA-N 0.000 description 2
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 2
- WVYXNIXAMZOZFK-UHFFFAOYSA-N diaziquone Chemical compound O=C1C(NC(=O)OCC)=C(N2CC2)C(=O)C(NC(=O)OCC)=C1N1CC1 WVYXNIXAMZOZFK-UHFFFAOYSA-N 0.000 description 2
- 229950002389 diaziquone Drugs 0.000 description 2
- YFAGHNZHGGCZAX-JKIFEVAISA-N dicloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl YFAGHNZHGGCZAX-JKIFEVAISA-N 0.000 description 2
- 229960001585 dicloxacillin Drugs 0.000 description 2
- 229960003974 diethylcarbamazine Drugs 0.000 description 2
- RCKMWOKWVGPNJF-UHFFFAOYSA-N diethylcarbamazine Chemical compound CCN(CC)C(=O)N1CCN(C)CC1 RCKMWOKWVGPNJF-UHFFFAOYSA-N 0.000 description 2
- 229960004875 difluprednate Drugs 0.000 description 2
- PZXJOHSZQAEJFE-UHFFFAOYSA-N dihydrobetulinic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(C)C)C5C4CCC3C21C PZXJOHSZQAEJFE-UHFFFAOYSA-N 0.000 description 2
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 2
- 229960004704 dihydroergotamine Drugs 0.000 description 2
- 125000005442 diisocyanate group Chemical group 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- OWQIUQKMMPDHQQ-UHFFFAOYSA-N dimethocaine Chemical compound CCN(CC)CC(C)(C)COC(=O)C1=CC=C(N)C=C1 OWQIUQKMMPDHQQ-UHFFFAOYSA-N 0.000 description 2
- 229950010160 dimethocaine Drugs 0.000 description 2
- OCUJLLGVOUDECM-UHFFFAOYSA-N dipivefrin Chemical compound CNCC(O)C1=CC=C(OC(=O)C(C)(C)C)C(OC(=O)C(C)(C)C)=C1 OCUJLLGVOUDECM-UHFFFAOYSA-N 0.000 description 2
- 229960000966 dipivefrine Drugs 0.000 description 2
- 229960002768 dipyridamole Drugs 0.000 description 2
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 2
- 229960004100 dirithromycin Drugs 0.000 description 2
- WLOHNSSYAXHWNR-NXPDYKKBSA-N dirithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H]2O[C@H](COCCOC)N[C@H]([C@@H]2C)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 WLOHNSSYAXHWNR-NXPDYKKBSA-N 0.000 description 2
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 2
- 208000002173 dizziness Diseases 0.000 description 2
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 description 2
- 229930188854 dolastatin Natural products 0.000 description 2
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 description 2
- 229960000895 doripenem Drugs 0.000 description 2
- IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 description 2
- 229960003933 dorzolamide Drugs 0.000 description 2
- 229960002955 doxapram Drugs 0.000 description 2
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 2
- 229950005454 doxifluridine Drugs 0.000 description 2
- 229950004203 droloxifene Drugs 0.000 description 2
- NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 description 2
- 229960004242 dronabinol Drugs 0.000 description 2
- 229950004683 drostanolone propionate Drugs 0.000 description 2
- 229960002866 duloxetine Drugs 0.000 description 2
- 229960003804 efavirenz Drugs 0.000 description 2
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 229950000549 elliptinium acetate Drugs 0.000 description 2
- 229960000325 emedastine Drugs 0.000 description 2
- KBUZBQVCBVDWKX-UHFFFAOYSA-N emedastine Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1N1CCCN(C)CC1 KBUZBQVCBVDWKX-UHFFFAOYSA-N 0.000 description 2
- 229960000366 emtricitabine Drugs 0.000 description 2
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 2
- 229950011487 enocitabine Drugs 0.000 description 2
- 229960002549 enoxacin Drugs 0.000 description 2
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 description 2
- 229960003337 entacapone Drugs 0.000 description 2
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 description 2
- 229960000980 entecavir Drugs 0.000 description 2
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 2
- 229960003449 epinastine Drugs 0.000 description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 2
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 2
- 229930013356 epothilone Natural products 0.000 description 2
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 2
- 229960004943 ergotamine Drugs 0.000 description 2
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 2
- 229960002770 ertapenem Drugs 0.000 description 2
- 229960004341 escitalopram Drugs 0.000 description 2
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 2
- ITSGNOIFAJAQHJ-BMFNZSJVSA-N esorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)C[C@H](C)O1 ITSGNOIFAJAQHJ-BMFNZSJVSA-N 0.000 description 2
- 229950002017 esorubicin Drugs 0.000 description 2
- CDCHDCWJMGXXRH-UHFFFAOYSA-N estazolam Chemical compound C=1C(Cl)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 CDCHDCWJMGXXRH-UHFFFAOYSA-N 0.000 description 2
- 229960002336 estazolam Drugs 0.000 description 2
- 229960001842 estramustine Drugs 0.000 description 2
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 102000015694 estrogen receptors Human genes 0.000 description 2
- 108010038795 estrogen receptors Proteins 0.000 description 2
- 229960001578 eszopiclone Drugs 0.000 description 2
- GBBSUAFBMRNDJC-INIZCTEOSA-N eszopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-INIZCTEOSA-N 0.000 description 2
- HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 description 2
- SZQIFWWUIBRPBZ-UHFFFAOYSA-N ethotoin Chemical compound O=C1N(CC)C(=O)NC1C1=CC=CC=C1 SZQIFWWUIBRPBZ-UHFFFAOYSA-N 0.000 description 2
- 229960003533 ethotoin Drugs 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 229960003976 etidocaine Drugs 0.000 description 2
- 229940009626 etidronate Drugs 0.000 description 2
- 229960005293 etodolac Drugs 0.000 description 2
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 2
- 229960005237 etoglucid Drugs 0.000 description 2
- 229960002049 etravirine Drugs 0.000 description 2
- PYGWGZALEOIKDF-UHFFFAOYSA-N etravirine Chemical compound CC1=CC(C#N)=CC(C)=C1OC1=NC(NC=2C=CC(=CC=2)C#N)=NC(N)=C1Br PYGWGZALEOIKDF-UHFFFAOYSA-N 0.000 description 2
- 229960000255 exemestane Drugs 0.000 description 2
- 238000013265 extended release Methods 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 229950011548 fadrozole Drugs 0.000 description 2
- 229960004396 famciclovir Drugs 0.000 description 2
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 2
- 229960000379 faropenem Drugs 0.000 description 2
- 229960001419 fenoprofen Drugs 0.000 description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 2
- 229960002428 fentanyl Drugs 0.000 description 2
- 229960000961 floxuridine Drugs 0.000 description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 2
- 229960000390 fludarabine Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 150000002222 fluorine compounds Chemical class 0.000 description 2
- 229960002074 flutamide Drugs 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 229960001447 fomivirsen Drugs 0.000 description 2
- XCWFZHPEARLXJI-UHFFFAOYSA-N fomivirsen Chemical compound C1C(N2C3=C(C(NC(N)=N3)=O)N=C2)OC(CO)C1OP(O)(=S)OCC1OC(N(C)C(=O)\N=C(\N)C=C)CC1OP(O)(=S)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=S)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=S)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=S)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=S)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=S)OCC1OC(N2C(N=C(N)C=C2)=O)CC1OP(O)(=S)OCC(C(C1)OP(S)(=O)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)OC1N1C=C(C)C(=O)NC1=O XCWFZHPEARLXJI-UHFFFAOYSA-N 0.000 description 2
- 229960000693 fosphenytoin Drugs 0.000 description 2
- 229960004783 fotemustine Drugs 0.000 description 2
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 2
- 229960002284 frovatriptan Drugs 0.000 description 2
- SIBNYOSJIXCDRI-SECBINFHSA-N frovatriptan Chemical compound C1=C(C(N)=O)[CH]C2=C(C[C@H](NC)CC3)C3=NC2=C1 SIBNYOSJIXCDRI-SECBINFHSA-N 0.000 description 2
- 229960003980 galantamine Drugs 0.000 description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
- 229940044658 gallium nitrate Drugs 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 235000008434 ginseng Nutrition 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 208000007345 glycogen storage disease Diseases 0.000 description 2
- 201000004502 glycogen storage disease II Diseases 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 229960003690 goserelin acetate Drugs 0.000 description 2
- 229960000642 grepafloxacin Drugs 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- 229960003242 halofantrine Drugs 0.000 description 2
- 229960003878 haloperidol Drugs 0.000 description 2
- 229960003132 halothane Drugs 0.000 description 2
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
- MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 description 2
- 229930193320 herbimycin Natural products 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 235000014304 histidine Nutrition 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 229960000930 hydroxyzine Drugs 0.000 description 2
- ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 description 2
- 229940015872 ibandronate Drugs 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 229960004801 imipramine Drugs 0.000 description 2
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 2
- 229950008097 improsulfan Drugs 0.000 description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 2
- 201000008319 inclusion body myositis Diseases 0.000 description 2
- 229960001936 indinavir Drugs 0.000 description 2
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
- UXZFQZANDVDGMM-UHFFFAOYSA-N iodoquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(I)C2=C1 UXZFQZANDVDGMM-UHFFFAOYSA-N 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 229960002672 isocarboxazid Drugs 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical class O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229960004958 ketotifen Drugs 0.000 description 2
- 206010023497 kuru Diseases 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229960002623 lacosamide Drugs 0.000 description 2
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 description 2
- 229960001627 lamivudine Drugs 0.000 description 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
- CWPGNVFCJOPXFB-UHFFFAOYSA-N lapachol Chemical compound C1=CC=C2C(=O)C(=O)C(CC=C(C)C)=C(O)C2=C1 CWPGNVFCJOPXFB-UHFFFAOYSA-N 0.000 description 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 2
- 229960001160 latanoprost Drugs 0.000 description 2
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 229940115286 lentinan Drugs 0.000 description 2
- 229960003881 letrozole Drugs 0.000 description 2
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 2
- 208000036546 leukodystrophy Diseases 0.000 description 2
- 229960004002 levetiracetam Drugs 0.000 description 2
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 2
- 229960000831 levobunolol Drugs 0.000 description 2
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 2
- 229960004502 levodopa Drugs 0.000 description 2
- 229960003376 levofloxacin Drugs 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229960004305 lodoxamide Drugs 0.000 description 2
- RVGLGHVJXCETIO-UHFFFAOYSA-N lodoxamide Chemical compound OC(=O)C(=O)NC1=CC(C#N)=CC(NC(=O)C(O)=O)=C1Cl RVGLGHVJXCETIO-UHFFFAOYSA-N 0.000 description 2
- 229960002247 lomustine Drugs 0.000 description 2
- YROQEQPFUCPDCP-UHFFFAOYSA-N losoxantrone Chemical compound OCCNCCN1N=C2C3=CC=CC(O)=C3C(=O)C3=C2C1=CC=C3NCCNCCO YROQEQPFUCPDCP-UHFFFAOYSA-N 0.000 description 2
- 229950008745 losoxantrone Drugs 0.000 description 2
- 229960001798 loteprednol Drugs 0.000 description 2
- YPZVAYHNBBHPTO-MXRBDKCISA-N loteprednol Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)OCCl)[C@@H]4[C@@H]3CCC2=C1 YPZVAYHNBBHPTO-MXRBDKCISA-N 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
- 229960000423 loxapine Drugs 0.000 description 2
- YQZBAXDVDZTKEQ-UHFFFAOYSA-N loxapine succinate Chemical compound [H+].[H+].[O-]C(=O)CCC([O-])=O.C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 YQZBAXDVDZTKEQ-UHFFFAOYSA-N 0.000 description 2
- 229960003640 mafenide Drugs 0.000 description 2
- 229940072082 magnesium salicylate Drugs 0.000 description 2
- MQXVYODZCMMZEM-ZYUZMQFOSA-N mannomustine Chemical compound ClCCNC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CNCCCl MQXVYODZCMMZEM-ZYUZMQFOSA-N 0.000 description 2
- 229950008612 mannomustine Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 2
- 229960001474 meclozine Drugs 0.000 description 2
- 229960001011 medrysone Drugs 0.000 description 2
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 2
- 229960003464 mefenamic acid Drugs 0.000 description 2
- 229960001962 mefloquine Drugs 0.000 description 2
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 2
- 229960004296 megestrol acetate Drugs 0.000 description 2
- 229960001728 melarsoprol Drugs 0.000 description 2
- 229960001929 meloxicam Drugs 0.000 description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
- 229960004640 memantine Drugs 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- GMHKMTDVRCWUDX-UHFFFAOYSA-N mephenytoin Chemical compound C=1C=CC=CC=1C1(CC)NC(=O)N(C)C1=O GMHKMTDVRCWUDX-UHFFFAOYSA-N 0.000 description 2
- 229960000906 mephenytoin Drugs 0.000 description 2
- ALARQZQTBTVLJV-UHFFFAOYSA-N mephobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)N(C)C1=O ALARQZQTBTVLJV-UHFFFAOYSA-N 0.000 description 2
- 229950009246 mepitiostane Drugs 0.000 description 2
- 229960002409 mepivacaine Drugs 0.000 description 2
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 description 2
- 229960004815 meprobamate Drugs 0.000 description 2
- 229960002260 meropenem Drugs 0.000 description 2
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 2
- SLVMESMUVMCQIY-UHFFFAOYSA-N mesoridazine Chemical compound CN1CCCCC1CCN1C2=CC(S(C)=O)=CC=C2SC2=CC=CC=C21 SLVMESMUVMCQIY-UHFFFAOYSA-N 0.000 description 2
- 229960000300 mesoridazine Drugs 0.000 description 2
- 229960001252 methamphetamine Drugs 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229960002057 metharbital Drugs 0.000 description 2
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 2
- 229960004083 methazolamide Drugs 0.000 description 2
- VJRAUFKOOPNFIQ-TVEKBUMESA-N methyl (1r,2r,4s)-4-[(2r,4s,5s,6s)-5-[(2s,4s,5s,6s)-5-[(2s,4s,5s,6s)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-2-ethyl-2,5,7,10-tetrahydroxy-6,11-dioxo-3,4-dihydro-1h-tetracene-1-carboxylat Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1C[C@H](O)[C@H](O)[C@H](C)O1 VJRAUFKOOPNFIQ-TVEKBUMESA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229960001344 methylphenidate Drugs 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 229960002704 metipranolol Drugs 0.000 description 2
- BLWNYSZZZWQCKO-UHFFFAOYSA-N metipranolol hydrochloride Chemical compound [Cl-].CC(C)[NH2+]CC(O)COC1=CC(C)=C(OC(C)=O)C(C)=C1C BLWNYSZZZWQCKO-UHFFFAOYSA-N 0.000 description 2
- 229960004503 metoclopramide Drugs 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 229960000282 metronidazole Drugs 0.000 description 2
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 2
- 229960000198 mezlocillin Drugs 0.000 description 2
- YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 208000027061 mild cognitive impairment Diseases 0.000 description 2
- 229960001785 mirtazapine Drugs 0.000 description 2
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 2
- 229960005485 mitobronitol Drugs 0.000 description 2
- 229960003539 mitoguazone Drugs 0.000 description 2
- MXWHMTNPTTVWDM-NXOFHUPFSA-N mitoguazone Chemical compound NC(N)=N\N=C(/C)\C=N\N=C(N)N MXWHMTNPTTVWDM-NXOFHUPFSA-N 0.000 description 2
- VFKZTMPDYBFSTM-GUCUJZIJSA-N mitolactol Chemical compound BrC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-GUCUJZIJSA-N 0.000 description 2
- 229950010913 mitolactol Drugs 0.000 description 2
- 229960000350 mitotane Drugs 0.000 description 2
- 229960001165 modafinil Drugs 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 229960004938 molindone Drugs 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 229960003702 moxifloxacin Drugs 0.000 description 2
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 2
- 201000000585 muscular atrophy Diseases 0.000 description 2
- 229940087004 mustargen Drugs 0.000 description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 2
- 229960000951 mycophenolic acid Drugs 0.000 description 2
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 2
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 2
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 description 2
- NJSMWLQOCQIOPE-OCHFTUDZSA-N n-[(e)-[10-[(e)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine Chemical compound N1CCN=C1N\N=C\C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N\NC1=NCCN1 NJSMWLQOCQIOPE-OCHFTUDZSA-N 0.000 description 2
- BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 229960004270 nabumetone Drugs 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229960003255 natamycin Drugs 0.000 description 2
- 235000010298 natamycin Nutrition 0.000 description 2
- 239000004311 natamycin Substances 0.000 description 2
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229960004398 nedocromil Drugs 0.000 description 2
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 2
- 229960001800 nefazodone Drugs 0.000 description 2
- VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 2
- 229960001002 nepafenac Drugs 0.000 description 2
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 description 2
- MQYXUWHLBZFQQO-UHFFFAOYSA-N nepehinol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C MQYXUWHLBZFQQO-UHFFFAOYSA-N 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 229960000808 netilmicin Drugs 0.000 description 2
- ZBGPYVZLYBDXKO-HILBYHGXSA-N netilmycin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@]([C@H](NC)[C@@H](O)CO1)(C)O)NCC)[C@H]1OC(CN)=CC[C@H]1N ZBGPYVZLYBDXKO-HILBYHGXSA-N 0.000 description 2
- 208000007538 neurilemmoma Diseases 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 2
- 229960002653 nilutamide Drugs 0.000 description 2
- 229960001420 nimustine Drugs 0.000 description 2
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 2
- 229960002480 nitazoxanide Drugs 0.000 description 2
- KGTDRFCXGRULNK-JYOBTZKQSA-N nogalamycin Chemical compound CO[C@@H]1[C@@](OC)(C)[C@@H](OC)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=C4[C@@]5(C)O[C@H]([C@H]([C@@H]([C@H]5O)N(C)C)O)OC4=C3C3=O)=C3C=C2[C@@H](C(=O)OC)[C@@](C)(O)C1 KGTDRFCXGRULNK-JYOBTZKQSA-N 0.000 description 2
- 229950009266 nogalamycin Drugs 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- 229960001158 nortriptyline Drugs 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
- CZDBNBLGZNWKMC-MWQNXGTOSA-N olivomycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1)O[C@H]1O[C@@H](C)[C@H](O)[C@@H](OC2O[C@@H](C)[C@H](O)[C@@H](O)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@H](O)[C@H](OC)[C@H](C)O1 CZDBNBLGZNWKMC-MWQNXGTOSA-N 0.000 description 2
- 229960004114 olopatadine Drugs 0.000 description 2
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 description 2
- 229950011093 onapristone Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 2
- 229960003752 oseltamivir Drugs 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 2
- 229960001019 oxacillin Drugs 0.000 description 2
- 229960002085 oxycodone Drugs 0.000 description 2
- 229960005118 oxymorphone Drugs 0.000 description 2
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 229960001057 paliperidone Drugs 0.000 description 2
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 2
- 229940046231 pamidronate Drugs 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 229960003274 paramethadione Drugs 0.000 description 2
- 208000002851 paranoid schizophrenia Diseases 0.000 description 2
- 229960002296 paroxetine Drugs 0.000 description 2
- HIANJWSAHKJQTH-UHFFFAOYSA-N pemirolast Chemical compound CC1=CC=CN(C2=O)C1=NC=C2C=1N=NNN=1 HIANJWSAHKJQTH-UHFFFAOYSA-N 0.000 description 2
- 229960004439 pemirolast Drugs 0.000 description 2
- 229960000761 pemoline Drugs 0.000 description 2
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 2
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 2
- 229960005301 pentazocine Drugs 0.000 description 2
- QIMGFXOHTOXMQP-GFAGFCTOSA-N peplomycin Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCCN[C@@H](C)C=1C=CC=CC=1)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C QIMGFXOHTOXMQP-GFAGFCTOSA-N 0.000 description 2
- 229950003180 peplomycin Drugs 0.000 description 2
- 229960004851 pergolide Drugs 0.000 description 2
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 2
- 229960000762 perphenazine Drugs 0.000 description 2
- 229960000482 pethidine Drugs 0.000 description 2
- WOIGZSBYKGQJGL-UHFFFAOYSA-N phenallymal Chemical compound C=1C=CC=CC=1C1(CC=C)C(=O)NC(=O)NC1=O WOIGZSBYKGQJGL-UHFFFAOYSA-N 0.000 description 2
- 229950010992 phenallymal Drugs 0.000 description 2
- 229960003877 pheneturide Drugs 0.000 description 2
- 229960003562 phentermine Drugs 0.000 description 2
- 229960002036 phenytoin Drugs 0.000 description 2
- 208000019899 phobic disease Diseases 0.000 description 2
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 2
- YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 description 2
- 229960003634 pimozide Drugs 0.000 description 2
- 229960002292 piperacillin Drugs 0.000 description 2
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 description 2
- 229960001045 piperocaine Drugs 0.000 description 2
- 229960000952 pipobroman Drugs 0.000 description 2
- NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 2
- NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 description 2
- 229950001100 piposulfan Drugs 0.000 description 2
- 229960002702 piroxicam Drugs 0.000 description 2
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 2
- 229960002797 pitavastatin Drugs 0.000 description 2
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 2
- 229960001237 podophyllotoxin Drugs 0.000 description 2
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 2
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000024 polymyxin B Polymers 0.000 description 2
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 description 2
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 2
- 229960005266 polymyxin b Drugs 0.000 description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 description 2
- 229960003089 pramipexole Drugs 0.000 description 2
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 2
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 description 2
- 229960004197 prasugrel Drugs 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
- 229960004694 prednimustine Drugs 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 229960001807 prilocaine Drugs 0.000 description 2
- MVFGUOIZUNYYSO-UHFFFAOYSA-N prilocaine Chemical compound CCCNC(C)C(=O)NC1=CC=CC=C1C MVFGUOIZUNYYSO-UHFFFAOYSA-N 0.000 description 2
- 229960005179 primaquine Drugs 0.000 description 2
- 229960002393 primidone Drugs 0.000 description 2
- DQMZLTXERSFNPB-UHFFFAOYSA-N primidone Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NCNC1=O DQMZLTXERSFNPB-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 229960005253 procyclidine Drugs 0.000 description 2
- 201000002241 progressive bulbar palsy Diseases 0.000 description 2
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 2
- 235000013930 proline Nutrition 0.000 description 2
- 229960003910 promethazine Drugs 0.000 description 2
- 229950003255 propoxycaine Drugs 0.000 description 2
- 229960002601 protriptyline Drugs 0.000 description 2
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 229960000996 pyrantel pamoate Drugs 0.000 description 2
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 2
- 229960000611 pyrimethamine Drugs 0.000 description 2
- 229960004431 quetiapine Drugs 0.000 description 2
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 2
- 229960000948 quinine Drugs 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 229960001150 ramelteon Drugs 0.000 description 2
- 229960003876 ranibizumab Drugs 0.000 description 2
- RUOKEQAAGRXIBM-GFCCVEGCSA-N rasagiline Chemical compound C1=CC=C2[C@H](NCC#C)CCC2=C1 RUOKEQAAGRXIBM-GFCCVEGCSA-N 0.000 description 2
- 229960000245 rasagiline Drugs 0.000 description 2
- BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 description 2
- 229960000460 razoxane Drugs 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 201000005070 reflex epilepsy Diseases 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 108010051412 reteplase Proteins 0.000 description 2
- 229960002917 reteplase Drugs 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- 229960000329 ribavirin Drugs 0.000 description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
- ATEBXHFBFRCZMA-VXTBVIBXSA-N rifabutin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC(=C2N3)C(=O)C=4C(O)=C5C)C)OC)C5=C1C=4C2=NC13CCN(CC(C)C)CC1 ATEBXHFBFRCZMA-VXTBVIBXSA-N 0.000 description 2
- 229960000885 rifabutin Drugs 0.000 description 2
- 229960001225 rifampicin Drugs 0.000 description 2
- 229960000888 rimantadine Drugs 0.000 description 2
- 229960001487 rimexolone Drugs 0.000 description 2
- QTTRZHGPGKRAFB-OOKHYKNYSA-N rimexolone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CC)(C)[C@@]1(C)C[C@@H]2O QTTRZHGPGKRAFB-OOKHYKNYSA-N 0.000 description 2
- 229960001534 risperidone Drugs 0.000 description 2
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 229960000425 rizatriptan Drugs 0.000 description 2
- TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 description 2
- 229950004892 rodorubicin Drugs 0.000 description 2
- 229960000371 rofecoxib Drugs 0.000 description 2
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 2
- MBABCNBNDNGODA-WPZDJQSSSA-N rolliniastatin 1 Natural products O1[C@@H]([C@@H](O)CCCCCCCCCC)CC[C@H]1[C@H]1O[C@@H]([C@H](O)CCCCCCCCCC[C@@H](O)CC=2C(O[C@@H](C)C=2)=O)CC1 MBABCNBNDNGODA-WPZDJQSSSA-N 0.000 description 2
- 229960001879 ropinirole Drugs 0.000 description 2
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 2
- 229960001549 ropivacaine Drugs 0.000 description 2
- NSFWWJIQIKBZMJ-PAGWOCKZSA-N roridin a Chemical compound C([C@@]12[C@]3(C)[C@H]4C[C@H]1O[C@@H]1C=C(C)CC[C@@]13COC(=O)[C@@H](O)[C@H](C)CCO[C@H](\C=C\C=C/C(=O)O4)[C@H](O)C)O2 NSFWWJIQIKBZMJ-PAGWOCKZSA-N 0.000 description 2
- 229960000672 rosuvastatin Drugs 0.000 description 2
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 2
- 229960003179 rotigotine Drugs 0.000 description 2
- KFQYTPMOWPVWEJ-INIZCTEOSA-N rotigotine Chemical compound CCCN([C@@H]1CC2=CC=CC(O)=C2CC1)CCC1=CC=CS1 KFQYTPMOWPVWEJ-INIZCTEOSA-N 0.000 description 2
- 229960005224 roxithromycin Drugs 0.000 description 2
- 229960003014 rufinamide Drugs 0.000 description 2
- POGQSBRIGCQNEG-UHFFFAOYSA-N rufinamide Chemical compound N1=NC(C(=O)N)=CN1CC1=C(F)C=CC=C1F POGQSBRIGCQNEG-UHFFFAOYSA-N 0.000 description 2
- 229940106773 sabril Drugs 0.000 description 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 2
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 description 2
- 206010039667 schwannoma Diseases 0.000 description 2
- RODXRVNMMDRFIK-UHFFFAOYSA-N scopoletin Chemical compound C1=CC(=O)OC2=C1C=C(OC)C(O)=C2 RODXRVNMMDRFIK-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229960002060 secobarbital Drugs 0.000 description 2
- KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 229960002073 sertraline Drugs 0.000 description 2
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 2
- 229960002078 sevoflurane Drugs 0.000 description 2
- DFEYYRMXOJXZRJ-UHFFFAOYSA-N sevoflurane Chemical compound FCOC(C(F)(F)F)C(F)(F)F DFEYYRMXOJXZRJ-UHFFFAOYSA-N 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 229950001403 sizofiran Drugs 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960004954 sparfloxacin Drugs 0.000 description 2
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 229960000268 spectinomycin Drugs 0.000 description 2
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 2
- 229950006315 spirogermanium Drugs 0.000 description 2
- ICXJVZHDZFXYQC-UHFFFAOYSA-N spongistatin 1 Natural products OC1C(O2)(O)CC(O)C(C)C2CCCC=CC(O2)CC(O)CC2(O2)CC(OC)CC2CC(=O)C(C)C(OC(C)=O)C(C)C(=C)CC(O2)CC(C)(O)CC2(O2)CC(OC(C)=O)CC2CC(=O)OC2C(O)C(CC(=C)CC(O)C=CC(Cl)=C)OC1C2C ICXJVZHDZFXYQC-UHFFFAOYSA-N 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 208000005809 status epilepticus Diseases 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- PVYJZLYGTZKPJE-UHFFFAOYSA-N streptonigrin Chemical compound C=1C=C2C(=O)C(OC)=C(N)C(=O)C2=NC=1C(C=1N)=NC(C(O)=O)=C(C)C=1C1=CC=C(OC)C(OC)=C1O PVYJZLYGTZKPJE-UHFFFAOYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 2
- 229960005256 sulbactam Drugs 0.000 description 2
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 2
- 229960004306 sulfadiazine Drugs 0.000 description 2
- 229960000654 sulfafurazole Drugs 0.000 description 2
- 229960005158 sulfamethizole Drugs 0.000 description 2
- VACCAVUAMIDAGB-UHFFFAOYSA-N sulfamethizole Chemical compound S1C(C)=NN=C1NS(=O)(=O)C1=CC=C(N)C=C1 VACCAVUAMIDAGB-UHFFFAOYSA-N 0.000 description 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
- 229960001940 sulfasalazine Drugs 0.000 description 2
- 108060007951 sulfatase Proteins 0.000 description 2
- 229960000894 sulindac Drugs 0.000 description 2
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 2
- 229960003708 sumatriptan Drugs 0.000 description 2
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 2
- 229960004492 suprofen Drugs 0.000 description 2
- 102000013498 tau Proteins Human genes 0.000 description 2
- 108010026424 tau Proteins Proteins 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 description 2
- 229960003865 tazobactam Drugs 0.000 description 2
- 229960001608 teicoplanin Drugs 0.000 description 2
- 229960005311 telbivudine Drugs 0.000 description 2
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 description 2
- 229960004576 temafloxacin Drugs 0.000 description 2
- 229960001114 temocillin Drugs 0.000 description 2
- BVCKFLJARNKCSS-DWPRYXJFSA-N temocillin Chemical compound N([C@]1(OC)C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(C(O)=O)C=1C=CSC=1 BVCKFLJARNKCSS-DWPRYXJFSA-N 0.000 description 2
- 229960000216 tenecteplase Drugs 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- 229960005353 testolactone Drugs 0.000 description 2
- BPEWUONYVDABNZ-DZBHQSCQSA-N testolactone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(OC(=O)CC4)[C@@H]4[C@@H]3CCC2=C1 BPEWUONYVDABNZ-DZBHQSCQSA-N 0.000 description 2
- 229960002372 tetracaine Drugs 0.000 description 2
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 2
- 239000004308 thiabendazole Substances 0.000 description 2
- 235000010296 thiabendazole Nutrition 0.000 description 2
- 229960004546 thiabendazole Drugs 0.000 description 2
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 description 2
- 229960002784 thioridazine Drugs 0.000 description 2
- 229960004659 ticarcillin Drugs 0.000 description 2
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 2
- VAMSVIZLXJOLHZ-QWFSEIHXSA-N tigemonam Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(=N/OCC(O)=O)\C1=CSC(N)=N1 VAMSVIZLXJOLHZ-QWFSEIHXSA-N 0.000 description 2
- 229950010206 tigemonam Drugs 0.000 description 2
- 229940019375 tiludronate Drugs 0.000 description 2
- 229960004605 timolol Drugs 0.000 description 2
- 229960005053 tinidazole Drugs 0.000 description 2
- 229960003087 tioguanine Drugs 0.000 description 2
- 229960005013 tiotixene Drugs 0.000 description 2
- 229960000838 tipranavir Drugs 0.000 description 2
- NZPXPXAGXYTROM-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(O)=C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)C1)CC1=CC=CC=C1 NZPXPXAGXYTROM-FYBSXPHGSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229960004603 tolcapone Drugs 0.000 description 2
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 2
- 229960001017 tolmetin Drugs 0.000 description 2
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
- 229960005267 tositumomab Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 2
- 229960004380 tramadol Drugs 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 229960002368 travoprost Drugs 0.000 description 2
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 2
- 229960003991 trazodone Drugs 0.000 description 2
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 2
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 2
- 229950001353 tretamine Drugs 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- PXSOHRWMIRDKMP-UHFFFAOYSA-N triaziquone Chemical compound O=C1C(N2CC2)=C(N2CC2)C(=O)C=C1N1CC1 PXSOHRWMIRDKMP-UHFFFAOYSA-N 0.000 description 2
- 229960002415 trichloroethylene Drugs 0.000 description 2
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- 229930013292 trichothecene Natural products 0.000 description 2
- 229960002324 trifluoperazine Drugs 0.000 description 2
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 2
- 229960003962 trifluridine Drugs 0.000 description 2
- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 description 2
- 229960001032 trihexyphenidyl Drugs 0.000 description 2
- GOZBHBFUQHMKQB-UHFFFAOYSA-N trimecaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=C(C)C=C1C GOZBHBFUQHMKQB-UHFFFAOYSA-N 0.000 description 2
- 229950002569 trimecaine Drugs 0.000 description 2
- IRYJRGCIQBGHIV-UHFFFAOYSA-N trimethadione Chemical compound CN1C(=O)OC(C)(C)C1=O IRYJRGCIQBGHIV-UHFFFAOYSA-N 0.000 description 2
- 229960004453 trimethadione Drugs 0.000 description 2
- FEZBIKUBAYAZIU-UHFFFAOYSA-N trimethobenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC=2C=CC(OCCN(C)C)=CC=2)=C1 FEZBIKUBAYAZIU-UHFFFAOYSA-N 0.000 description 2
- 229960004161 trimethobenzamide Drugs 0.000 description 2
- 229960001099 trimetrexate Drugs 0.000 description 2
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 2
- 229960002431 trimipramine Drugs 0.000 description 2
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 2
- 229950000212 trioxifene Drugs 0.000 description 2
- 229960000875 trofosfamide Drugs 0.000 description 2
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 2
- 229960005041 troleandomycin Drugs 0.000 description 2
- LQCLVBQBTUVCEQ-QTFUVMRISA-N troleandomycin Chemical compound O1[C@@H](C)[C@H](OC(C)=O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](C)C(=O)O[C@H](C)[C@H](C)[C@H](OC(C)=O)[C@@H](C)C(=O)[C@@]2(OC2)C[C@H](C)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)OC(C)=O)[C@H]1C LQCLVBQBTUVCEQ-QTFUVMRISA-N 0.000 description 2
- 229960000497 trovafloxacin Drugs 0.000 description 2
- WVPSKSLAZQPAKQ-CDMJZVDBSA-N trovafloxacin Chemical compound C([C@H]1[C@@H]([C@H]1C1)N)N1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=NC=1N2C1=CC=C(F)C=C1F WVPSKSLAZQPAKQ-CDMJZVDBSA-N 0.000 description 2
- 229950010147 troxacitabine Drugs 0.000 description 2
- RXRGZNYSEHTMHC-BQBZGAKWSA-N troxacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)OC1 RXRGZNYSEHTMHC-BQBZGAKWSA-N 0.000 description 2
- HDZZVAMISRMYHH-LITAXDCLSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O HDZZVAMISRMYHH-LITAXDCLSA-N 0.000 description 2
- 229950009811 ubenimex Drugs 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 229940093257 valacyclovir Drugs 0.000 description 2
- 229960002149 valganciclovir Drugs 0.000 description 2
- 229960000653 valrubicin Drugs 0.000 description 2
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 2
- 229960003165 vancomycin Drugs 0.000 description 2
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 2
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 229960005318 vigabatrin Drugs 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- 229960004355 vindesine Drugs 0.000 description 2
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 2
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 2
- 229960002066 vinorelbine Drugs 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 229960001771 vorozole Drugs 0.000 description 2
- XLMPPFTZALNBFS-INIZCTEOSA-N vorozole Chemical compound C1([C@@H](C2=CC=C3N=NN(C3=C2)C)N2N=CN=C2)=CC=C(Cl)C=C1 XLMPPFTZALNBFS-INIZCTEOSA-N 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 229960004664 xaliproden Drugs 0.000 description 2
- WJJYZXPHLSLMGE-UHFFFAOYSA-N xaliproden Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C4C=CC=CC4=CC=3)CC=2)=C1 WJJYZXPHLSLMGE-UHFFFAOYSA-N 0.000 description 2
- 229960004010 zaleplon Drugs 0.000 description 2
- HUNXMJYCHXQEGX-UHFFFAOYSA-N zaleplon Chemical compound CCN(C(C)=O)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C#N)=C1 HUNXMJYCHXQEGX-UHFFFAOYSA-N 0.000 description 2
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 2
- 229960001028 zanamivir Drugs 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
- 229960000607 ziprasidone Drugs 0.000 description 2
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
- 229960001360 zolmitriptan Drugs 0.000 description 2
- ULSDMUVEXKOYBU-ZDUSSCGKSA-N zolmitriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C[C@H]1COC(=O)N1 ULSDMUVEXKOYBU-ZDUSSCGKSA-N 0.000 description 2
- 229960002911 zonisamide Drugs 0.000 description 2
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 2
- 229960000641 zorubicin Drugs 0.000 description 2
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 1
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
- YXTKHLHCVFUPPT-YYFJYKOTSA-N (2s)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid;(1r,2r)-1,2-dimethanidylcyclohexane;5-fluoro-1h-pyrimidine-2,4-dione;oxalic acid;platinum(2+) Chemical compound [Pt+2].OC(=O)C(O)=O.[CH2-][C@@H]1CCCC[C@H]1[CH2-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 YXTKHLHCVFUPPT-YYFJYKOTSA-N 0.000 description 1
- FLWWDYNPWOSLEO-HQVZTVAUSA-N (2s)-2-[[4-[1-(2-amino-4-oxo-1h-pteridin-6-yl)ethyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1C(C)N(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FLWWDYNPWOSLEO-HQVZTVAUSA-N 0.000 description 1
- LMGGOGHEVZMZCU-FGJMKEJPSA-N (2s,4s)-4-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,7,12-tetrahydroxy-6,11-dioxo-3,4-dihydro-1h-tetracene-2-carboxylic acid Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(O)=O)C1 LMGGOGHEVZMZCU-FGJMKEJPSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- TVIRNGFXQVMMGB-OFWIHYRESA-N (3s,6r,10r,13e,16s)-16-[(2r,3r,4s)-4-chloro-3-hydroxy-4-phenylbutan-2-yl]-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H](O)[C@@H](Cl)C=2C=CC=CC=2)C/C=C/C(=O)N1 TVIRNGFXQVMMGB-OFWIHYRESA-N 0.000 description 1
- XRBSKUSTLXISAB-UHFFFAOYSA-N (7R,7'R,8R,8'R)-form-Podophyllic acid Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C(CO)C2C(O)=O)=C1 XRBSKUSTLXISAB-UHFFFAOYSA-N 0.000 description 1
- AESVUZLWRXEGEX-DKCAWCKPSA-N (7S,9R)-7-[(2S,4R,5R,6R)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione iron(3+) Chemical compound [Fe+3].COc1cccc2C(=O)c3c(O)c4C[C@@](O)(C[C@H](O[C@@H]5C[C@@H](N)[C@@H](O)[C@@H](C)O5)c4c(O)c3C(=O)c12)C(=O)CO AESVUZLWRXEGEX-DKCAWCKPSA-N 0.000 description 1
- NOPNWHSMQOXAEI-PUCKCBAPSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-(2,3-dihydropyrrol-1-yl)-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCC=C1 NOPNWHSMQOXAEI-PUCKCBAPSA-N 0.000 description 1
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 1
- YRMCBQLZVBXOSJ-PCFSSPOYSA-N (e)-3-[(6r,6as)-4-hydroxy-6-methoxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide Chemical compound CO[C@H]1NC2=C(O)C(C)=CC=C2C(=O)N2C=C(\C=C\C(N)=O)C[C@@H]12 YRMCBQLZVBXOSJ-PCFSSPOYSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- ICYXLUKKODFXAM-UHFFFAOYSA-N 1,3-oxazolidine-2,4-dione Chemical compound O1C(NC(C1)=O)=O.O1C(NC(C1)=O)=O ICYXLUKKODFXAM-UHFFFAOYSA-N 0.000 description 1
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 1
- YZGAZHWDQGGMJN-UHFFFAOYSA-N 1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4-oxo-2,3-dihydroquinoline-3-carboxylic acid Chemical compound FC1=C2N(CC)CC(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 YZGAZHWDQGGMJN-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- JVJUWEFOGFCHKR-UHFFFAOYSA-N 2-(diethylamino)ethyl 1-(3,4-dimethylphenyl)cyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=C(C)C(C)=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 JVJUWEFOGFCHKR-UHFFFAOYSA-N 0.000 description 1
- NYWSLZMTZNODJM-MCGDBQAWSA-N 2-[5-[(4e,20e)-35-butyl-19-[(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-10,12,14,16,18,22,26,30,34-nonahydroxy-3,5,21,33-tetramethyl-36-oxo-1-oxacyclohexatriaconta-4,20-dien-2-yl]-4-hydroxyhexyl]guanidine Chemical compound OC1CC(O)CC(O)CC(O)CC(O)CCCC\C(C)=C\C(C)C(C(C)C(O)CCCN=C(N)N)OC(=O)C(CCCC)C(O)C(C)CCC(O)CCCC(O)CCCC(O)\C(C)=C\C1O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 NYWSLZMTZNODJM-MCGDBQAWSA-N 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- ALHXTYGCVYTWIY-UHFFFAOYSA-N 2-amino-3,7-dihydropurine-6-thione Chemical compound N1C(N)=NC(=S)C2=C1N=CN2.N1C(N)=NC(=S)C2=C1N=CN2 ALHXTYGCVYTWIY-UHFFFAOYSA-N 0.000 description 1
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 description 1
- 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
- 229940127239 5 Hydroxytryptamine receptor antagonist Drugs 0.000 description 1
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- 229960005538 6-diazo-5-oxo-L-norleucine Drugs 0.000 description 1
- YCWQAMGASJSUIP-YFKPBYRVSA-N 6-diazo-5-oxo-L-norleucine Chemical compound OC(=O)[C@@H](N)CCC(=O)C=[N+]=[N-] YCWQAMGASJSUIP-YFKPBYRVSA-N 0.000 description 1
- AOJJSUZBOXZQNB-UHFFFAOYSA-N 7-[(4-amino-5-hydroxy-6-methyl-2-oxanyl)oxy]-6,9,11-trihydroxy-9-(2-hydroxy-1-oxoethyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione Chemical compound C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(=O)CO)CC1OC1CC(N)C(O)C(C)O1 AOJJSUZBOXZQNB-UHFFFAOYSA-N 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 1
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
- 208000023769 AA amyloidosis Diseases 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000006772 Acid Ceramidase Human genes 0.000 description 1
- 108020005296 Acid Ceramidase Proteins 0.000 description 1
- 206010052075 Acquired epileptic aphasia Diseases 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 101710153593 Albumin A Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
- 101710181800 Aminopeptidase 1 Proteins 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 241000224489 Amoeba Species 0.000 description 1
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000014654 Aromatase Human genes 0.000 description 1
- 108010078554 Aromatase Proteins 0.000 description 1
- 229940122815 Aromatase inhibitor Drugs 0.000 description 1
- 101710205806 Artemin Proteins 0.000 description 1
- 102100022146 Arylsulfatase A Human genes 0.000 description 1
- 102100031491 Arylsulfatase B Human genes 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 108010078286 Ataxins Proteins 0.000 description 1
- 102000014461 Ataxins Human genes 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 208000007333 Brain Concussion Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- PYMDEDHDQYLBRT-DRIHCAFSSA-N Buserelin acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 PYMDEDHDQYLBRT-DRIHCAFSSA-N 0.000 description 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 208000022526 Canavan disease Diseases 0.000 description 1
- VBGLYOIFKLUMQG-UHFFFAOYSA-N Cannabinol Chemical compound C1=C(C)C=C2C3=C(O)C=C(CCCCC)C=C3OC(C)(C)C2=C1 VBGLYOIFKLUMQG-UHFFFAOYSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- 102100028892 Cardiotrophin-1 Human genes 0.000 description 1
- 244000132059 Carica parviflora Species 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 108010036867 Cerebroside-Sulfatase Proteins 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 description 1
- 208000000532 Chronic Brain Injury Diseases 0.000 description 1
- VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010053398 Clonic convulsion Diseases 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- XXGMIHXASFDFSM-UHFFFAOYSA-N Delta9-tetrahydrocannabinol Natural products CCCCCc1cc2OC(C)(C)C3CCC(=CC3c2c(O)c1O)C XXGMIHXASFDFSM-UHFFFAOYSA-N 0.000 description 1
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
- 206010012397 Depression suicidal Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- AUGQEEXBDZWUJY-UHFFFAOYSA-N Diacetoxyscirpenol Natural products CC(=O)OCC12CCC(C)=CC1OC1C(O)C(OC(C)=O)C2(C)C11CO1 AUGQEEXBDZWUJY-UHFFFAOYSA-N 0.000 description 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
- XEHFSYYAGCUKEN-UHFFFAOYSA-N Dihydroscopoletin Natural products C1CC(=O)OC2=C1C=C(OC)C(O)=C2 XEHFSYYAGCUKEN-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 229940094659 Dopamine reuptake inhibitor Drugs 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 201000007547 Dravet syndrome Diseases 0.000 description 1
- 206010013643 Drop attacks Diseases 0.000 description 1
- 206010013752 Drug withdrawal convulsions Diseases 0.000 description 1
- 229930193152 Dynemicin Natural products 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 108010032976 Enfuvirtide Proteins 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000289659 Erinaceidae Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 229930189413 Esperamicin Natural products 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 208000033149 Farber disease Diseases 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- 201000009010 Frontal lobe epilepsy Diseases 0.000 description 1
- 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
- 229940098788 GABA receptor antagonist Drugs 0.000 description 1
- 108091007911 GSKs Proteins 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 1
- 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 1
- 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 244000060234 Gmelina philippensis Species 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241000606841 Haemophilus sp. Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 108010034145 Helminth Proteins Proteins 0.000 description 1
- 241000224421 Heterolobosea Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102000016871 Hexosaminidase A Human genes 0.000 description 1
- 108010053317 Hexosaminidase A Proteins 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 102000004627 Iduronidase Human genes 0.000 description 1
- 108010003381 Iduronidase Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 201000008189 Juvenile absence epilepsy Diseases 0.000 description 1
- 206010071082 Juvenile myoclonic epilepsy Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- JLERVPBPJHKRBJ-UHFFFAOYSA-N LY 117018 Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(O)C=C2S1 JLERVPBPJHKRBJ-UHFFFAOYSA-N 0.000 description 1
- 201000005802 Landau-Kleffner Syndrome Diseases 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 description 1
- 102100032693 Leucine-rich repeat serine/threonine-protein kinase 2 Human genes 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 208000026709 Liddle syndrome Diseases 0.000 description 1
- 241000480130 Liusus Species 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 208000008948 Menkes Kinky Hair Syndrome Diseases 0.000 description 1
- 208000012583 Menkes disease Diseases 0.000 description 1
- AJXPJJZHWIXJCJ-UHFFFAOYSA-N Methsuximide Chemical compound O=C1N(C)C(=O)CC1(C)C1=CC=CC=C1 AJXPJJZHWIXJCJ-UHFFFAOYSA-N 0.000 description 1
- 102100030335 Midkine Human genes 0.000 description 1
- 108010092801 Midkine Proteins 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
- 101000823042 Mus musculus Amyloid-beta precursor protein Proteins 0.000 description 1
- 101000835089 Mus musculus Transferrin receptor protein 1 Proteins 0.000 description 1
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 101710099863 N-acetylgalactosamine-6-sulfatase Proteins 0.000 description 1
- 102100031688 N-acetylgalactosamine-6-sulfatase Human genes 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 1
- 101150064037 NGF gene Proteins 0.000 description 1
- 241001440871 Neisseria sp. Species 0.000 description 1
- 240000002853 Nelumbo nucifera Species 0.000 description 1
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 1
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 1
- 101710204212 Neocarzinostatin Proteins 0.000 description 1
- 102000010803 Netrins Human genes 0.000 description 1
- 108010063605 Netrins Proteins 0.000 description 1
- 102000014413 Neuregulin Human genes 0.000 description 1
- 108050003475 Neuregulin Proteins 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 102000003683 Neurotrophin-4 Human genes 0.000 description 1
- 102100033857 Neurotrophin-4 Human genes 0.000 description 1
- 102100021584 Neurturin Human genes 0.000 description 1
- 108010015406 Neurturin Proteins 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 208000000224 Night Terrors Diseases 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- KYYIDSXMWOZKMP-UHFFFAOYSA-N O-desmethylvenlafaxine Chemical compound C1CCCCC1(O)C(CN(C)C)C1=CC=C(O)C=C1 KYYIDSXMWOZKMP-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 108010093625 Opioid Peptides Proteins 0.000 description 1
- 102000001490 Opioid Peptides Human genes 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- VREZDOWOLGNDPW-MYVCAWNPSA-N Pancratistatin Natural products O=C1N[C@H]2[C@H](O)[C@H](O)[C@H](O)[C@H](O)[C@@H]2c2c1c(O)c1OCOc1c2 VREZDOWOLGNDPW-MYVCAWNPSA-N 0.000 description 1
- VREZDOWOLGNDPW-ALTGWBOUSA-N Pancratistatin Chemical compound C1=C2[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)[C@@H]3NC(=O)C2=C(O)C2=C1OCO2 VREZDOWOLGNDPW-ALTGWBOUSA-N 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 102100036660 Persephin Human genes 0.000 description 1
- 206010034759 Petit mal epilepsy Diseases 0.000 description 1
- XPFRXWCVYUEORT-UHFFFAOYSA-N Phenacemide Chemical compound NC(=O)NC(=O)CC1=CC=CC=C1 XPFRXWCVYUEORT-UHFFFAOYSA-N 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100039277 Pleiotrophin Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 206010036049 Polycystic ovaries Diseases 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 108010036933 Presenilin-1 Proteins 0.000 description 1
- 102000012412 Presenilin-1 Human genes 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 1
- ZGUGWUXLJSTTMA-UHFFFAOYSA-N Promazinum Chemical class C1=CC=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZGUGWUXLJSTTMA-UHFFFAOYSA-N 0.000 description 1
- ROSXARVHJNYYDO-UHFFFAOYSA-N Propyliodone Chemical compound CCCOC(=O)CN1C=C(I)C(=O)C(I)=C1 ROSXARVHJNYYDO-UHFFFAOYSA-N 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000334216 Proteus sp. Species 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589774 Pseudomonas sp. Species 0.000 description 1
- 241000508269 Psidium Species 0.000 description 1
- 208000037012 Psychomotor seizures Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 1
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- OWPCHSCAPHNHAV-UHFFFAOYSA-N Rhizoxin Natural products C1C(O)C2(C)OC2C=CC(C)C(OC(=O)C2)CC2CC2OC2C(=O)OC1C(C)C(OC)C(C)=CC=CC(C)=CC1=COC(C)=N1 OWPCHSCAPHNHAV-UHFFFAOYSA-N 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 102000017852 Saposin Human genes 0.000 description 1
- 108050007079 Saposin Proteins 0.000 description 1
- 101710184528 Scaffolding protein Proteins 0.000 description 1
- 206010039811 Secondary amyloidosis Diseases 0.000 description 1
- 108010086019 Secretin Proteins 0.000 description 1
- 102100037505 Secretin Human genes 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- 206010041010 Sleep terror Diseases 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 239000004268 Sodium erythorbin Substances 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000194022 Streptococcus sp. Species 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 102100025292 Stress-induced-phosphoprotein 1 Human genes 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- PJSFRIWCGOHTNF-UHFFFAOYSA-N Sulphormetoxin Chemical compound COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC PJSFRIWCGOHTNF-UHFFFAOYSA-N 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 206010048327 Supranuclear palsy Diseases 0.000 description 1
- BXFOFFBJRFZBQZ-QYWOHJEZSA-N T-2 toxin Chemical compound C([C@@]12[C@]3(C)[C@H](OC(C)=O)[C@@H](O)[C@H]1O[C@H]1[C@]3(COC(C)=O)C[C@@H](C(=C1)C)OC(=O)CC(C)C)O2 BXFOFFBJRFZBQZ-QYWOHJEZSA-N 0.000 description 1
- 101710199430 TATA-box-binding protein 2 Proteins 0.000 description 1
- 208000034799 Tauopathies Diseases 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 1
- 102000005488 Thioesterase Human genes 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- 102000002070 Transferrins Human genes 0.000 description 1
- 108010015865 Transferrins Proteins 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 description 1
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 1
- 208000006657 Unverricht-Lundborg syndrome Diseases 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 1
- ZYVSOIYQKUDENJ-ASUJBHBQSA-N [(2R,3R,4R,6R)-6-[[(6S,7S)-6-[(2S,4R,5R,6R)-4-[(2R,4R,5R,6R)-4-[(2S,4S,5S,6S)-5-acetyloxy-4-hydroxy-4,6-dimethyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-7-[(3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-4,10-dihydroxy-3-methyl-5-oxo-7,8-dihydro-6H-anthracen-2-yl]oxy]-4-[(2R,4R,5R,6R)-4-hydroxy-5-methoxy-6-methyloxan-2-yl]oxy-2-methyloxan-3-yl] acetate Chemical class COC([C@@H]1Cc2cc3cc(O[C@@H]4C[C@@H](O[C@@H]5C[C@@H](O)[C@@H](OC)[C@@H](C)O5)[C@H](OC(C)=O)[C@@H](C)O4)c(C)c(O)c3c(O)c2C(=O)[C@H]1O[C@H]1C[C@@H](O[C@@H]2C[C@@H](O[C@H]3C[C@](C)(O)[C@@H](OC(C)=O)[C@H](C)O3)[C@H](O)[C@@H](C)O2)[C@H](O)[C@@H](C)O1)C(=O)[C@@H](O)[C@@H](C)O ZYVSOIYQKUDENJ-ASUJBHBQSA-N 0.000 description 1
- SPJCRMJCFSJKDE-ZWBUGVOYSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] 2-[4-[bis(2-chloroethyl)amino]phenyl]acetate Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 SPJCRMJCFSJKDE-ZWBUGVOYSA-N 0.000 description 1
- IFJUINDAXYAPTO-UUBSBJJBSA-N [(8r,9s,13s,14s,17s)-17-[2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butanoyloxy]acetyl]oxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] benzoate Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4OC(=O)COC(=O)CCCC=1C=CC(=CC=1)N(CCCl)CCCl)C)CC2=CC=3OC(=O)C1=CC=CC=C1 IFJUINDAXYAPTO-UUBSBJJBSA-N 0.000 description 1
- CGZHFISPYUSNJI-QLERUFQFSA-N [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=N1.[C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=N1 Chemical compound [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=N1.[C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=N1 CGZHFISPYUSNJI-QLERUFQFSA-N 0.000 description 1
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 description 1
- USDJGQLNFPZEON-UHFFFAOYSA-N [[4,6-bis(hydroxymethylamino)-1,3,5-triazin-2-yl]amino]methanol Chemical compound OCNC1=NC(NCO)=NC(NCO)=N1 USDJGQLNFPZEON-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 208000003554 absence epilepsy Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- LCJHLOJKAAQLQW-UHFFFAOYSA-N acetic acid;ethane Chemical compound CC.CC(O)=O LCJHLOJKAAQLQW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229930188522 aclacinomycin Natural products 0.000 description 1
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
- 229960004176 aclarubicin Drugs 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229960001997 adefovir Drugs 0.000 description 1
- 229960003205 adefovir dipivoxil Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- VWYANPOOORUCFJ-UHFFFAOYSA-N alpha-Fernenol Chemical compound CC1(C)C(O)CCC2(C)C3=CCC4(C)C5CCC(C(C)C)C5(C)CCC4(C)C3CCC21 VWYANPOOORUCFJ-UHFFFAOYSA-N 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- VQKFNUFAXTZWDK-UHFFFAOYSA-N alpha-methylfuran Natural products CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- 239000002380 aminotransferase inhibitor Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 229960001301 amobarbital Drugs 0.000 description 1
- 210000003001 amoeba Anatomy 0.000 description 1
- 229960001830 amprenavir Drugs 0.000 description 1
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 1
- 229940098184 amytal Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001466 anti-adreneric effect Effects 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000001062 anti-nausea Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940125684 antimigraine agent Drugs 0.000 description 1
- 239000002282 antimigraine agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000003418 antiprogestin Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 229960002610 apraclonidine Drugs 0.000 description 1
- IEJXVRYNEISIKR-UHFFFAOYSA-N apraclonidine Chemical compound ClC1=CC(N)=CC(Cl)=C1NC1=NCCN1 IEJXVRYNEISIKR-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960004823 armodafinil Drugs 0.000 description 1
- YFGHCGITMMYXAQ-LJQANCHMSA-N armodafinil Chemical compound C=1C=CC=CC=1C([S@](=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-LJQANCHMSA-N 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229930101531 artemisinin Natural products 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 229940091616 bacitracin / polymyxin b Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 238000013542 behavioral therapy Methods 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- 229950005567 benzodepa Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- VFIUCBTYGKMLCM-UHFFFAOYSA-N benzyl n-[bis(aziridin-1-yl)phosphoryl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NP(=O)(N1CC1)N1CC1 VFIUCBTYGKMLCM-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- FWLORMQUOWCQPO-UHFFFAOYSA-N benzyl-dimethyl-octadecylazanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 FWLORMQUOWCQPO-UHFFFAOYSA-N 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229940126587 biotherapeutics Drugs 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000005098 blood-cerebrospinal fluid barrier Anatomy 0.000 description 1
- 210000004155 blood-retinal barrier Anatomy 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 210000004782 brain capillary endothelium Anatomy 0.000 description 1
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 1
- 229960002719 buserelin Drugs 0.000 description 1
- 229960005064 buserelin acetate Drugs 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 description 1
- 229960003453 cannabinol Drugs 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 230000004858 capillary barrier Effects 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 108010041776 cardiotrophin 1 Proteins 0.000 description 1
- 108010047060 carzinophilin Proteins 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229960000603 cefalotin Drugs 0.000 description 1
- HOGISBSFFHDTRM-GHXIOONMSA-N cefdaloxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/O)\C1=CSC(N)=N1 HOGISBSFFHDTRM-GHXIOONMSA-N 0.000 description 1
- 229950006550 cefdaloxime Drugs 0.000 description 1
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 description 1
- 229960005090 cefpodoxime Drugs 0.000 description 1
- 229960000484 ceftazidime Drugs 0.000 description 1
- ORFOPKXBNMVMKC-DWVKKRMSSA-N ceftazidime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 ORFOPKXBNMVMKC-DWVKKRMSSA-N 0.000 description 1
- 229960001991 ceftizoxime Drugs 0.000 description 1
- NNULBSISHYWZJU-LLKWHZGFSA-N ceftizoxime Chemical compound N([C@@H]1C(N2C(=CCS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 NNULBSISHYWZJU-LLKWHZGFSA-N 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000003153 cholinolytic effect Effects 0.000 description 1
- 210000002987 choroid plexus Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 description 1
- 229960000724 cidofovir Drugs 0.000 description 1
- 229960004588 cilostazol Drugs 0.000 description 1
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 208000028502 clonic seizure Diseases 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 108010089438 cryptophycin 1 Proteins 0.000 description 1
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 description 1
- 108010090203 cryptophycin 8 Proteins 0.000 description 1
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Natural products NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 229960005107 darunavir Drugs 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 229960001623 desvenlafaxine Drugs 0.000 description 1
- 208000013257 developmental and epileptic encephalopathy Diseases 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
- ADYPXRFPBQGGAH-WVVAGBSPSA-N dihydroergotoxine Chemical compound CS(O)(=O)=O.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C=3C=CC=C4NC=C(C=34)C2)C1)C)C1=CC=CC=C1 ADYPXRFPBQGGAH-WVVAGBSPSA-N 0.000 description 1
- 229940120500 dihydroergotoxine Drugs 0.000 description 1
- 229960000691 diiodohydroxyquinoline Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000005182 dinitrobenzenes Chemical class 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 229940028937 divalproex sodium Drugs 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000000221 dopamine uptake inhibitor Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 201000009028 early myoclonic encephalopathy Diseases 0.000 description 1
- 229960002759 eflornithine Drugs 0.000 description 1
- 238000001678 elastic recoil detection analysis Methods 0.000 description 1
- XOPYFXBZMVTEJF-PDACKIITSA-N eleutherobin Chemical compound C(/[C@H]1[C@H](C(=CC[C@@H]1C(C)C)C)C[C@@H]([C@@]1(C)O[C@@]2(C=C1)OC)OC(=O)\C=C\C=1N=CN(C)C=1)=C2\CO[C@@H]1OC[C@@H](O)[C@@H](O)[C@@H]1OC(C)=O XOPYFXBZMVTEJF-PDACKIITSA-N 0.000 description 1
- XOPYFXBZMVTEJF-UHFFFAOYSA-N eleutherobin Natural products C1=CC2(OC)OC1(C)C(OC(=O)C=CC=1N=CN(C)C=1)CC(C(=CCC1C(C)C)C)C1C=C2COC1OCC(O)C(O)C1OC(C)=O XOPYFXBZMVTEJF-UHFFFAOYSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 229960002062 enfuvirtide Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- JOZGNYDSEBIJDH-UHFFFAOYSA-N eniluracil Chemical compound O=C1NC=C(C#C)C(=O)N1 JOZGNYDSEBIJDH-UHFFFAOYSA-N 0.000 description 1
- 229950010213 eniluracil Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000000219 ependymocyte Anatomy 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229950002973 epitiostanol Drugs 0.000 description 1
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- FQHMMOGHDWAXDI-WUQHHHCFSA-N ergoloid mesylate Chemical compound CS(O)(=O)=O.C([C@H]1[C@]2(O)O3)CCN1C(=O)[C@H](C)N2C(=O)[C@]3(C(C)C)NC(=O)[C@H]1CN(C)[C@H](CC=2C3=C4C=CC=C3NC=2)[C@@H]4C1 FQHMMOGHDWAXDI-WUQHHHCFSA-N 0.000 description 1
- LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 229960004447 ethchlorvynol Drugs 0.000 description 1
- 229960002767 ethosuximide Drugs 0.000 description 1
- QSRLNKCNOLVZIR-KRWDZBQOSA-N ethyl (2s)-2-[[2-[4-[bis(2-chloroethyl)amino]phenyl]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 QSRLNKCNOLVZIR-KRWDZBQOSA-N 0.000 description 1
- 208000038004 exacerbated respiratory disease Diseases 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960003472 felbamate Drugs 0.000 description 1
- WKGXYQFOCVYPAC-UHFFFAOYSA-N felbamate Chemical compound NC(=O)OCC(COC(N)=O)C1=CC=CC=C1 WKGXYQFOCVYPAC-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 206010016629 fibroma Diseases 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- 229960001048 fluorometholone Drugs 0.000 description 1
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 229940064302 folacin Drugs 0.000 description 1
- 229960004421 formestane Drugs 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960003142 fosamprenavir Drugs 0.000 description 1
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 1
- 229960005102 foscarnet Drugs 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 description 1
- 229950002508 gantenerumab Drugs 0.000 description 1
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 150000008271 glucosaminides Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 229960004905 gramicidin Drugs 0.000 description 1
- ZWCXYZRRTRDGQE-SORVKSEFSA-N gramicidina Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 ZWCXYZRRTRDGQE-SORVKSEFSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 244000000013 helminth Species 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- SYECJBOWSGTPLU-UHFFFAOYSA-N hexane-1,1-diamine Chemical compound CCCCCC(N)N SYECJBOWSGTPLU-UHFFFAOYSA-N 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000057593 human F8 Human genes 0.000 description 1
- 229940088013 hycamtin Drugs 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000001709 ictal effect Effects 0.000 description 1
- 208000034287 idiopathic generalized susceptibility to 7 epilepsy Diseases 0.000 description 1
- 150000002454 idoses Chemical class 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 229960003162 iloperidone Drugs 0.000 description 1
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229960002182 imipenem Drugs 0.000 description 1
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940055742 indium-111 Drugs 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 102000009634 interleukin-1 receptor antagonist activity proteins Human genes 0.000 description 1
- 108040001669 interleukin-1 receptor antagonist activity proteins Proteins 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229940065638 intron a Drugs 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229960002418 ivermectin Drugs 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 229960001320 lapatinib ditosylate Drugs 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004288 levobupivacaine Drugs 0.000 description 1
- LEBVLXFERQHONN-INIZCTEOSA-N levobupivacaine Chemical compound CCCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-INIZCTEOSA-N 0.000 description 1
- SIEYLFHKZGLBNX-NTISSMGPSA-N levobupivacaine hydrochloride (anhydrous) Chemical compound [Cl-].CCCC[NH+]1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C SIEYLFHKZGLBNX-NTISSMGPSA-N 0.000 description 1
- 208000013469 light sensitivity Diseases 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960001451 lisdexamfetamine Drugs 0.000 description 1
- VOBHXZCDAVEXEY-JSGCOSHPSA-N lisdexamfetamine Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)CC1=CC=CC=C1 VOBHXZCDAVEXEY-JSGCOSHPSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960002422 lomefloxacin Drugs 0.000 description 1
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 229940087857 lupron Drugs 0.000 description 1
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 229960004710 maraviroc Drugs 0.000 description 1
- GSNHKUDZZFZSJB-QYOOZWMWSA-N maraviroc Chemical compound CC(C)C1=NN=C(C)N1[C@@H]1C[C@H](N2CC[C@H](NC(=O)C3CCC(F)(F)CC3)C=3C=CC=CC=3)CC[C@H]2C1 GSNHKUDZZFZSJB-QYOOZWMWSA-N 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229960000299 mazindol Drugs 0.000 description 1
- 229960003439 mebendazole Drugs 0.000 description 1
- BAXLBXFAUKGCDY-UHFFFAOYSA-N mebendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CC=C1 BAXLBXFAUKGCDY-UHFFFAOYSA-N 0.000 description 1
- OPXLLQIJSORQAM-UHFFFAOYSA-N mebendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1C(=O)C1=CC=CC=C1 OPXLLQIJSORQAM-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 229960003729 mesuximide Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- 238000001690 micro-dialysis Methods 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 208000012268 mitochondrial disease Diseases 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- FOYWNSCCNCUEPU-UHFFFAOYSA-N mopidamol Chemical compound C12=NC(N(CCO)CCO)=NC=C2N=C(N(CCO)CCO)N=C1N1CCCCC1 FOYWNSCCNCUEPU-UHFFFAOYSA-N 0.000 description 1
- 229950010718 mopidamol Drugs 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 208000028492 myoclonic seizure Diseases 0.000 description 1
- AZBFJBJXUQUQLF-UHFFFAOYSA-N n-(1,5-dimethylpyrrolidin-3-yl)pyrrolidine-1-carboxamide Chemical compound C1N(C)C(C)CC1NC(=O)N1CCCC1 AZBFJBJXUQUQLF-UHFFFAOYSA-N 0.000 description 1
- GPXLMGHLHQJAGZ-JTDSTZFVSA-N nafcillin Chemical compound C1=CC=CC2=C(C(=O)N[C@@H]3C(N4[C@H](C(C)(C)S[C@@H]43)C(O)=O)=O)C(OCC)=CC=C21 GPXLMGHLHQJAGZ-JTDSTZFVSA-N 0.000 description 1
- 229960000515 nafcillin Drugs 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 229940087524 nardil Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229940097998 neurotrophin 4 Drugs 0.000 description 1
- 229960000689 nevirapine Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- YMVWGSQGCWCDGW-UHFFFAOYSA-N nitracrine Chemical compound C1=CC([N+]([O-])=O)=C2C(NCCCN(C)C)=C(C=CC=C3)C3=NC2=C1 YMVWGSQGCWCDGW-UHFFFAOYSA-N 0.000 description 1
- 229950008607 nitracrine Drugs 0.000 description 1
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
- 229960001454 nitrazepam Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229940053973 novocaine Drugs 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229950005848 olivomycin Drugs 0.000 description 1
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960001816 oxcarbazepine Drugs 0.000 description 1
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229960000402 palivizumab Drugs 0.000 description 1
- VREZDOWOLGNDPW-UHFFFAOYSA-N pancratistatine Natural products C1=C2C3C(O)C(O)C(O)C(O)C3NC(=O)C2=C(O)C2=C1OCO2 VREZDOWOLGNDPW-UHFFFAOYSA-N 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 229960003407 pegaptanib Drugs 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 229960003931 peginterferon alfa-2b Drugs 0.000 description 1
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 108010070453 persephin Proteins 0.000 description 1
- 208000022821 personality disease Diseases 0.000 description 1
- 229960003396 phenacemide Drugs 0.000 description 1
- 229960000964 phenelzine Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229940041153 polymyxins Drugs 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 229950004406 porfiromycin Drugs 0.000 description 1
- 229940068586 prezista Drugs 0.000 description 1
- NYWSLZMTZNODJM-SDUQVVOESA-N primycin Natural products CCCC[C@H]1[C@H](O)[C@H](C)CC[C@@H](O)CCC[C@@H](O)CCC[C@@H](O)C(=C[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)C[C@H](O)C[C@@H](O)C[C@H](O)C[C@H](O)CCCCC(=C[C@@H](C)[C@@H](OC1=O)[C@H](C)[C@H](O)CCCNC(=N)N)C)C NYWSLZMTZNODJM-SDUQVVOESA-N 0.000 description 1
- 229950010664 primycin Drugs 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 230000001072 progestational effect Effects 0.000 description 1
- 230000003623 progesteronic effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 229960005385 proguanil Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- ABBQGOCHXSPKHJ-WUKNDPDISA-N prontosil Chemical compound NC1=CC(N)=CC=C1\N=N\C1=CC=C(S(N)(=O)=O)C=C1 ABBQGOCHXSPKHJ-WUKNDPDISA-N 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003927 propyliodone Drugs 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 229940035613 prozac Drugs 0.000 description 1
- WOLQREOUPKZMEX-UHFFFAOYSA-N pteroyltriglutamic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C=C1 WOLQREOUPKZMEX-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 229930183339 qinghaosu Natural products 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960004742 raltegravir Drugs 0.000 description 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
- 229960002185 ranimustine Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229940047431 recombinate Drugs 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- OWPCHSCAPHNHAV-LMONGJCWSA-N rhizoxin Chemical compound C/C([C@H](OC)[C@@H](C)[C@@H]1C[C@H](O)[C@]2(C)O[C@@H]2/C=C/[C@@H](C)[C@]2([H])OC(=O)C[C@@](C2)(C[C@@H]2O[C@H]2C(=O)O1)[H])=C\C=C\C(\C)=C\C1=COC(C)=N1 OWPCHSCAPHNHAV-LMONGJCWSA-N 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229940089617 risedronate Drugs 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- IMUQLZLGWJSVMV-UOBFQKKOSA-N roridin A Natural products CC(O)C1OCCC(C)C(O)C(=O)OCC2CC(=CC3OC4CC(OC(=O)C=C/C=C/1)C(C)(C23)C45CO5)C IMUQLZLGWJSVMV-UOBFQKKOSA-N 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 229930182947 sarcodictyin Natural products 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- FWYIBGHGBOVPNL-UHFFFAOYSA-N scopoletin Natural products COC=1C=C2C=CC(OC2=C(C1)O)=O FWYIBGHGBOVPNL-UHFFFAOYSA-N 0.000 description 1
- 208000008864 scrapie Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229960002101 secretin Drugs 0.000 description 1
- OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229960003928 sodium oxybate Drugs 0.000 description 1
- MOSCXNXKSOHVSQ-UHFFFAOYSA-M sodium;2-hydroxybutanoate Chemical compound [Na+].CCC(O)C([O-])=O MOSCXNXKSOHVSQ-UHFFFAOYSA-M 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000003755 striatonigral degeneration Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- 229950008188 sulfamidochrysoidine Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- BSUXZTMOMIFYBF-FFWSUHOLSA-N tabtoxinine beta-lactam Chemical compound OC(=O)[C@@H](N)CC[C@]1(O)CNC1=O BSUXZTMOMIFYBF-FFWSUHOLSA-N 0.000 description 1
- LJVAJPDWBABPEJ-PNUFFHFMSA-N telithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)[C@@H](C)C(=O)O[C@@H]([C@]2(OC(=O)N(CCCCN3C=C(N=C3)C=3C=NC=CC=3)[C@@H]2[C@@H](C)C(=O)[C@H](C)C[C@@]1(C)OC)C)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O LJVAJPDWBABPEJ-PNUFFHFMSA-N 0.000 description 1
- 229960003250 telithromycin Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 201000008914 temporal lobe epilepsy Diseases 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- 229940063650 terramycin Drugs 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 229940127228 tetracyclic antidepressant Drugs 0.000 description 1
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 108020002982 thioesterase Proteins 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- YFTWHEBLORWGNI-UHFFFAOYSA-N tiamiprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC(N)=NC2=C1NC=N2 YFTWHEBLORWGNI-UHFFFAOYSA-N 0.000 description 1
- 229950011457 tiamiprine Drugs 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 1
- 208000028500 tonic seizure Diseases 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 208000009174 transverse myelitis Diseases 0.000 description 1
- 229960003741 tranylcypromine Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 229960004560 triaziquone Drugs 0.000 description 1
- LZAJKCZTKKKZNT-PMNGPLLRSA-N trichothecene Chemical compound C12([C@@]3(CC[C@H]2OC2C=C(CCC23C)C)C)CO1 LZAJKCZTKKKZNT-PMNGPLLRSA-N 0.000 description 1
- 150000003327 trichothecene derivatives Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- KVJXBPDAXMEYOA-CXANFOAXSA-N trilostane Chemical compound OC1=C(C#N)C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@@]32O[C@@H]31 KVJXBPDAXMEYOA-CXANFOAXSA-N 0.000 description 1
- 229960001670 trilostane Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 229960001055 uracil mustard Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 229960003636 vidarabine Drugs 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-OUBTZVSYSA-N water-17o Chemical compound [17OH2] XLYOFNOQVPJJNP-OUBTZVSYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229960000523 zalcitabine Drugs 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2881—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD71
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明涉及结合血脑屏障上的受体(R/BBB)的血脑屏障穿梭体及其使用方法。
Description
本申请是2013年8月26日提交的发明专利申请201380042265.1的分案申请。
技术领域
本发明涉及结合血脑屏障上的受体(R/BBB)的血脑屏障穿梭体及其使用方法。
背景技术
神经疾病药物(例如具有低脑穿透的大生物治疗药物或小分子药物)的脑穿透,受广泛的且不可渗透的血脑屏障(BBB)以及神经血管单元(NVU)中的其它细胞组分严格限制。已经试验了许多克服该阻碍的策略,并且一种策略是利用在脑毛细血管内皮上表达的内源性受体所介导的胞吞转运途径。已经针对这些受体设计了重组蛋白诸如单克隆抗体或肽,以实现受体介导的生物治疗剂向脑的递送。但是,使脑摄取最大化、同时使脑内皮细胞(BEC)内的错误分选(miss-sorting)以及在BEC中的某些细胞器(特别是导致生物治疗剂的降解的细胞器)内的积累程度最小化的策略仍未得到探究。
单克隆抗体和其它生物治疗剂在治疗中枢神经系统(CNS)的病理学中具有巨大治疗潜力。但是,它们进入脑中的途径被BBB阻止。以前的研究已经阐明,非常小百分比(大约0.1%)的在血流中注射的IgG能够穿透进CNS隔室中(Felgenhauer,Klin.Wschr.52:1158-1164(1974))。由于抗体在CNS内的低浓度,这必然会限制任何药理学作用。
因此,需要使神经疾病药物穿过BBB的递送系统,以将药物有效地穿梭进脑中。
发明内容
在第一方面,本发明提供了一种血脑屏障穿梭体,其包含脑效应物实体、接头和一个结合血脑屏障受体的单价结合实体,其中所述接头将所述效应物实体与所述结合血脑屏障受体的单价结合实体偶联。
在所述血脑屏障穿梭体的一个特定实施方案中,所述结合血脑屏障受体的单价结合实体选自蛋白、多肽和肽。
在所述血脑屏障穿梭体的一个特定实施方案中,所述结合血脑屏障受体的单价结合实体包含选自以下的分子:血脑屏障受体配体、scFv、Fv、sFab、VHH,优选sFab。
在所述血脑屏障穿梭体的一个特定实施方案中,所述血脑受体选自转铁蛋白受体、胰岛素受体、胰岛素样生长因子受体、低密度脂蛋白受体相关的蛋白8、低密度脂蛋白受体相关的蛋白1和结合肝素的表皮生长因子样生长因子,优选转铁蛋白受体。
在所述血脑屏障穿梭体的一个特定实施方案中,所述结合血脑屏障受体的单价结合实体包含一个针对转铁蛋白受体的scFab,更具体地是识别被包含在Seq.Id.No.14、15或16的氨基酸序列中的转铁蛋白受体内的表位的scFab。
在所述血脑屏障穿梭体的一个特定实施方案中,所述脑效应物实体选自神经疾病药物、神经营养因子、生长因子、酶、细胞毒性剂、针对脑靶标的抗体、针对脑靶标的单克隆抗体、针对脑靶标的肽。
在所述血脑屏障穿梭体的一个特定实施方案中,所述脑靶标选自β-分泌酶1、Aβ、表皮生长因子、表皮生长因子受体2、Tau、磷酸化的Tau、载脂蛋白E4、α突触核蛋白、α突触核蛋白的寡聚片段、CD20、亨廷顿蛋白、朊病毒蛋白、富含亮氨酸的重复序列激酶2、帕金蛋白、早老蛋白2、γ分泌酶、死亡受体6、淀粉样蛋白前体蛋白、p75神经营养因子受体和胱天蛋白酶6。
在所述血脑屏障穿梭体的一个特定实施方案中,所述脑效应物实体选自蛋白、多肽和肽。
在所述血脑屏障穿梭体的一个特定实施方案中,所述结合血脑受体的单价结合实体选自蛋白、多肽和肽,且所述单价结合实体通过所述接头偶联至所述脑效应物实体的C-末端。
在所述血脑屏障穿梭体的一个特定实施方案中,所述脑效应物实体包含针对脑靶标的全长抗体,优选全长IgG。
在所述血脑屏障穿梭体的一个特定实施方案中,所述血脑屏障穿梭体包含作为脑效应物实体的全长IgG抗体、接头和一个作为结合血脑受体的单价结合实体的scFab,其中所述scFab通过所述接头偶联至所述IgG抗体的重链之一的Fc部分的C-末端。
在所述血脑屏障穿梭体的一个特定实施方案中,所述效应物实体是针对Aβ的全长抗体。
在所述血脑屏障穿梭体的一个特定实施方案中,所述针对Aβ的抗体包含:(a)H-CDR1,其包含Seq.Id.No.5的氨基酸序列,(b)H-CDR2,其包含Seq.Id.No.6的氨基酸序列,(c)H-CDR3,其包含Seq.Id.No.7的氨基酸序列,(d)L-CDR1,其包含Seq.Id.No.8的氨基酸序列,(e)L-CDR2,其包含Seq.Id.No.9的氨基酸序列,和(f)L-CDR3,其包含Seq.Id.No.10的氨基酸序列。
在所述血脑屏障穿梭体的一个特定实施方案中,所述针对Aβ的抗体包含:包含Seq.Id.No.11的氨基酸序列的VH结构域和包含Seq.Id.No.12的氨基酸序列的VL结构域。
在血脑屏障穿梭体的一个特定实施方案中,所述效应物实体是针对Aβ的全长抗体,且所述单价结合实体是针对转铁蛋白受体的scFab,更具体地是识别被包含在Seq.Id.No.14、15或16的氨基酸序列中的转铁蛋白受体内的表位的scFab。
在所述血脑屏障穿梭体的一个特定实施方案中,所述针对脑靶标的血脑屏障穿梭体的抗体的第一重链包含第一二聚化模块,且所述针对脑靶标的血脑屏障穿梭体的抗体的第二重链包含第二二聚化模块,从而允许所述两个重链的异源二聚化。
在所述血脑屏障穿梭体的一个特定实施方案中,根据突出物进入孔洞(knobsinto holes)策略,所述针对脑靶标的血脑屏障穿梭体的抗体的第一重链的第一二聚化模块包含突出物,且所述针对脑靶标的血脑屏障穿梭体的抗体的第二重链的二聚化模块包含孔洞。
在所述血脑屏障穿梭体的一个特定实施方案中,所述效应物实体是针对磷酸化的Tau的全长抗体,且所述单价结合实体是一个针对转铁蛋白受体的scFab。
在所述血脑屏障穿梭体的一个特定实施方案中,所述效应物实体是针对α突触核蛋白的全长抗体,且所述单价结合实体是一个针对转铁蛋白受体的scFab。
在所述血脑屏障穿梭体的一个特定实施方案中,所述接头是肽接头,优选地是具有至少25个氨基酸长度的氨基酸序列的肽,更优选地具有30-50个氨基酸的长度,特别地所述接头是(G4S)6G2或(G4S)4。
本发明的下述3个实施方案涉及血脑屏障穿梭体,其中所述脑效应物实体是蛋白、多肽或肽,前提条件是,所述脑效应物实体不是全长抗体,尤其全长IgG。
在所述血脑屏障穿梭体的一个特定实施方案中,所述结合血脑屏障受体的单价结合实体包含CH2-CH3 Ig实体和一个结合血脑屏障受体的sFab,其中所述sFab通过第二接头偶联至CH2-CH3 Ig实体的C-末端。
在所述血脑屏障穿梭体的一个特定实施方案中,所述血脑屏障穿梭体包含脑效应物实体、接头、CH2-CH3 Ig结构域、第二接头和一个结合血脑屏障受体的sFab,其中所述脑效应物实体通过第一接头偶联至CH2-CH3 Ig结构域的N-末端,且所述sFab通过第二接头偶联至CH2-CH3 Ig结构域的C-末端。
在所述血脑屏障穿梭体的一个特定实施方案中,所述CH2-CH3 Ig实体是CH2-CH3IgG实体。
此外,本发明涉及编码本发明的血脑屏障穿梭体的分离的核酸、包含编码所述血脑屏障穿梭体的分离的核酸的宿主细胞、和包含所述血脑屏障穿梭体的药物制剂。
本发明的血脑屏障穿梭体可以用作药物,特别地,它可以用于治疗神经疾病例如阿尔茨海默病。
本发明的血脑屏障穿梭体可以用于运输所述脑效应物实体穿过血脑屏障。
在一个特定实施方案中,本发明的血脑屏障穿梭体的IgG抗体的重链(其在Fc部分的C-末端处偶联至scFab,所述scFab作为结合血脑屏障受体的单价结合实体)具有下述结构:
●IgG重链,
●接头,其将IgG重链的Fc部分的C-末端偶联至scFab的VL结构域的N-末端,
●scFab的可变轻链结构域(VL)和C-κ轻链结构域,
●接头,其将scFab的C-κ轻链结构域的C-末端偶联至scFab的VH结构域的N-末端,
●scFab抗体的可变重链结构域(VH)和IgG CH3重链结构域。
在第二方面,本发明提供了一种运输脑效应物实体穿过血脑屏障的融合蛋白,所述融合蛋白包含CH2-CH3 Ig实体、接头和一个针对血脑屏障受体的sFab,其中所述sFab通过所述接头偶联至CH2-CH3 Ig实体的C-末端。
在本发明的融合蛋白的一个特定实施方案中,本发明的融合蛋白进一步包含在CH2-CH3 Ig实体的N-末端处的接头,以将所述脑效应物实体偶联至CH2-CH3 Ig实体的N-末端。
在本发明的融合蛋白的一个特定实施方案中,所述脑效应物实体选自神经疾病药物、神经营养因子、生长因子、酶、细胞毒性剂、选自scFv、Fv、scFab、Fab、VHH、F(ab’)2的针对脑靶标的抗体片段或肽。
在本发明的融合蛋白的一个特定实施方案中,所述针对血脑屏障受体的sFab是针对转铁蛋白受体的sFab,优选地是识别被包含在Seq.Id.No.14、15或16的氨基酸序列中的转铁蛋白受体内的表位的scFab。
在本发明的融合蛋白的一个特定实施方案中,所述接头是肽接头,尤其是具有至少15个氨基酸长度的氨基酸序列的肽,更优选地具有20-50个氨基酸的长度,最特别地所述接头具有氨基酸序列(G4S)6G2(Seq.Id.No.13)或(G4S)4(Seq.Id.No.17)。
在本发明的融合蛋白的一个特定实施方案中,所述CH2-CH3 Ig实体是CH2-CH3IgG实体。
此外,本发明提供了一种编码本发明的融合蛋白的分离的核酸和包含编码本发明的融合蛋白的核酸的宿主细胞。
在第三方面,本发明提供了一种缀合物,其包含本发明的融合蛋白和脑效应物实体,所述脑效应物实体通过接头偶联至本发明的融合蛋白的CH2-CH3 Ig实体的N-末端。
在本发明的缀合物的一个特定实施方案中,所述脑效应物实体是神经营养因子,且其中将所述神经营养因子偶联至CH2-CH3 Ig实体的N-末端的接头是肽接头。
此外,本发明提供了包含本发明的缀合物和药用载体的药物制剂,所述缀合物作为药物的用途,尤其是所述缀合物用于治疗神经变性疾病、尤其是阿尔茨海默病的用途。
附图说明
图1:在实施例中使用的不同形式的血脑屏障穿梭体(融合蛋白)。1A:针对Aβ的IgG(mAb31)。1B:针对TfR的单Fab(sFab),其偶联至针对Aβ的IgG(mAb31)的Fc部分。1C:针对TfR的双Fab(dFab),其偶联至针对Aβ的IgG(mAb31)的Fc部分。所述scFab结构与IgG抗体的重链的C-末端融合。
图2:融合蛋白对Aβ结构的结合性能。使用ELISA方案测量结合亲和力,所述ELISA方案表明,所述Fab构建体已经保留Aβ结合性能。mAb31-8D3构建体与Aβ纤丝的结合。尽管8D3(空心正方形)不会结合固定化的Aβ纤丝,但是mAb31-8D3-dFab(实心正方形)、mAb31-8D3-sFab(空心三角形)和mAb31(实心三角形)以可比较的亲和力结合。
图3:所述构建体对转铁蛋白受体(TfR)的结合性能。使用ELISA方案测量结合亲和力,所述ELISA方案表明,仅Fab构建体结合转铁蛋白受体(TfR),且双Fab构建体由于二价结合模式而具有稍微更高的表观亲和力。mAb31-8D3构建体与mTfR的结合。尽管mAb31(实心三角形)不会结合固定化的mTfR,但是mAb31-8D3-dFab(实心正方形)的结合亲和力与8D3亲本抗体(空心正方形)的结合亲和力相当。单价构建体mAb31-8D3-sFab(空心三角形)显示出中间结合亲和力。
图4:抗-Aβ单克隆抗体mAb31(图4A)、单Fab mAb31(与mAb31的C-末端融合的单Fab)(图4B)和双Fab mAb31(与mAb31的C-末端融合的双Fab)(图4C)的斑块染色。将构建体注射进PS2APP小鼠(n=3/构建体),单次静脉内给药10mg/kg,然后在给药后8小时进行脑灌注。分析包括斑块结合的免疫组织化学和共焦显微术。数据表明,仅单Fab-mAb31构建体能够穿过BBB并结合斑块。该图显示了得自所有动物的脑的一个代表性区域。
图5:显示了双Fab-mAb31构建体的定量。在所有3只治疗的动物的3个不同区域(每种构建体共计9个区域)定量斑块和毛细血管染色。数据表明,仅双Fab-mAb31构建体与mAb31相比存在毛细血管的增加。没有检测到在斑块处(在脑内)增加的双Fab-mAb31水平。以10mg/kg给药后8h,mab31(HEK对照)相对于双Fab-mab3的定量。
图6:显示了单Fab-mAb31构建体的定量。在所有3只治疗的动物的3个不同区域(每种构建体共计9个区域)定量斑块和毛细血管染色。数据表明,单Fab-mAb31构建体与mAb31相比存在斑块的大量增加。荧光信号的定量指示,单Fab-mAb31与mAb31构建体相比超过50倍的增加。单Fab-mAb31构建体与mAb31相比也存在毛细血管中的短暂染色,从而指示穿过BBB。以10mg/kg给药后8h和以25mg/kg给药后24h,mab31(HEK对照)相对于单Fab-mab31的定量。
图7:2种不同剂量的抗-Aβ单克隆抗体mAb31和非常低剂量的单Fab mAb31(与mAb31的C-末端融合的单Fab)的斑块染色。将构建体注射进PS2APP小鼠(n=3/构建体)中,单次静脉内给药,然后在给药后的不同时间点进行脑灌注。分析包括斑块结合的免疫组织化学和共焦显微术。数据表明,仅单Fab-mAb31构建体能够穿过BBB并结合斑块。对于单Fab-mAb31构建体而言,脑暴露是非常快速的,并且斑块染色从单次施用持续超过至少1周。
图8:用单Fab-mab31或双Fab-mAb31处理的TfR的细胞表面表达的定量。双Fab-mAb31构建体对转铁蛋白受体(TfR)的细胞表面减量调节。将表达TfR的脑内皮细胞与单Fab-mAb31构建体(图8A)或双Fab-mAb31构建体(图8B)一起温育24小时。仅双Fab-mAb31构建体降低了细胞表面表达的TfR的水平。
图9:用单Fab-mab31或双Fab-mAb31处理的TfR的体内细胞运输。在体内研究毛细血管和斑块染色的早期时间点。sFab-MAb31(图9A)和dFab-MAb31(图9B)在注射后15分钟将脑脉管系统染色,它们的分布没有差异。注射后8小时,sFab-MAb31达到实质并将淀粉样蛋白斑块染色(箭头,图9C),而dFab-MAb31停留在脑脉管系统内,类似于15分钟时间点(图9D)。对于dFab-MAb31而言,在实质中没有检测到淀粉样蛋白斑块。
图10:用单Fab-mab31或双Fab-mAb31处理的TfR的体内细胞运输。为了控制在研究中使用的所有构建体的完整性,使用MAb31(图10A)、sFab-MAb31(图10B)或dFab-MAB31(图10C),进行18个月小鼠APP转基因脑冷冻切片的染色。图10D显示了对照的结果。结果表明,所有3种构建体检测到转基因小鼠的脑中的淀粉样蛋白斑块。
图11:用单Fab-mab31处理的TfR的体内细胞运输。对体内处理过的样品的高分辨率共焦显微术表明,sFab-MAb31没有将脑毛细血管的腔侧染色,但是被包含在囊泡样结构(其穿过内皮细胞的腔膜)内和内皮细胞胞质溶胶内。在图11中的箭头指示在内皮细胞细胞核的近腔侧上含有sFab-MAb31构建体的囊泡。这些数据提示,sFab-MAb31可以进入脑内皮细胞并穿过脉管系统和到达脑的实质空间内的淀粉样蛋白斑块(与图9A和C对比)。
图12:用双Fab-mab31处理的TfR的体内细胞运输。对体内处理过的样品的高分辨率共焦显微术表明,dFab-MAb31没有将脑毛细血管的腔侧染色,但是被包含在囊泡样结构(其穿过内皮细胞的腔膜)内和内皮细胞胞质溶胶内。在图12中的箭头指示在内皮细胞细胞核的近腔侧上含有dFab-MAb31构建体的囊泡。这些数据提示,dFab-MAb31可以进入脑内皮细胞,但是被捕集,不能穿过脉管系统,且因此不能到达脑的实质空间内的淀粉样蛋白斑块(与图图9B和D对比)。
图13:静脉内施用以后的脑暴露和斑块染色。图13A:将mAb31、dFab和sFab构建体以10mg/kg静脉内地注射进PS2APP转基因动物,在注射后8小时将动物灌注和处死。dFab与mAb31相比,没有检测到斑块染色的显著增加。对于sFab构建体,基于来自检测抗体的在555nm的荧光强度,检测到比亲本mAb31高55倍的斑块染色。注射后8小时,mAb31(图13B)、dFab(图13C)和sFab(图13D)在皮质中的代表性免疫组织化学染色。dFab仅显示微血管染色,而sFab广泛地将淀粉样蛋白-β斑块染色。图13E:证实了与2mg/kg和10mg/kg mAb31相比,低剂量的sFab构建体(2.66mg/kg)会快速地且显著地到达脑中的斑块。sFab构建体的靶标啮合在注射后持续超过至少1周。免疫组织化学染色显示了2mg/kg的mAb31(图13F)和2.66mg/kg的sFab(图13G)在注射后7天的斑块染色。
图14:在通过14次每周静脉内注射治疗的、带有斑块的PS2APP小鼠中的慢性研究的体内效力。分别对于低剂量mAb31、中剂量mAb31、低剂量sFab和中剂量sFab(图14A-D),显示了在研究结束时,与残余斑块结合的施用构建体的靶斑块结合。在斑块的免疫组织化学染色以后,显示了皮质和海马的定量形态测定分析(图14E)。在4.5个月龄时处死的未治疗的动物的斑块负载被显示为在研究开始时的淀粉样变性的基线水平。与在媒介物治疗的动物中观察到的进行性斑块形成相比,在用中剂量sFab治疗以后,斑块数目的显著减少是显而易见的;减少的斑块形成的趋势甚至出现在低剂量sFab。因而,sFab构建体显著减少了皮质和海马中的斑块数目。斑块尺寸的分析揭示了斑块数目的减少,对于小斑块尺寸而言是最显著的。*p≤0.05,**p≤0.01,***p≤0.001。
图15:具有与Fc C-端融合的TfR scFab片段的抗体多聚体没有诱导ADCC。通过定量LDH释放,测量NK92介导的BA/F3小鼠红白血病细胞的杀死。仅多聚体构建体(其具有结合TfR的Fab部分,呈“常规”“N-端至Fc”取向)诱导显著的ADCC,而呈相反取向的脑穿梭构建体是沉默的。
图16:针对转铁蛋白受体的scFab 8D3结合小鼠转铁蛋白受体的细胞外结构域中的3个不同肽。通过抗体的化学发光检测,揭示了有3个氨基酸重叠的抗体8D3-15聚体肽的结合,所述抗体在携带固定化的mTfR肽的CelluSpot载玻片上温育。框:被8D3结合的肽#373、374和376(Seq.Id.No.15、16和17)。
具体实施方式
定义
“血脑屏障”或“BBB”是指外周循环与脑和脊髓之间的生理屏障,其由脑毛细血管内皮质膜内的紧密连接部形成,从而建立限制分子(甚至非常小的分子如尿素(60道尔顿))运输进脑中的紧密屏障。脑内的BBB、脊髓内的血液-脊髓屏障和视网膜内的血液-视网膜屏障,是CNS内的相连毛细血管屏障,并且在本文中被统称为血脑屏障或BBB。BBB还包括血液-CSF屏障(脉络丛),其中屏障由室管膜细胞而不是毛细血管内皮细胞构成。
突出物进入孔洞二聚化模块和它们在抗体工程中的应用描述在:Carter P.;Ridgway J.B.B.;Presta L.G.:Immunotechnology,Volume 2,Number 1,1996年2月,第73-73页(1))。
“中枢神经系统”或“CNS”是指控制身体功能的神经组织的复合体,并且包括脑和脊髓。
“血脑屏障受体”(本文中简写为“R/BBB”)是在脑内皮细胞上表达的细胞外膜连接的受体蛋白,其能够将分子运输穿过BBB或者用于运输外源施用的分子。本文中R/BBB的例子包括:转铁蛋白受体(TfR)、胰岛素受体、胰岛素样生长因子受体(IGF-R)、低密度脂蛋白受体(包括但不限于低密度脂蛋白受体相关的蛋白1(LRP1)和低密度脂蛋白受体相关的蛋白8(LRP8))、和结合肝素的表皮生长因子样生长因子(HB-EGF)。本文中的一种示例性的R/BBB是转铁蛋白受体(TfR)。
“脑效应物实体”是指要穿过BBB运输至脑的分子。效应物实体通常具有希望递送至脑的特征性治疗活性。效应物实体包括神经疾病药物和细胞毒性剂例如肽、蛋白和抗体,尤其是针对脑靶标的单克隆抗体或其片段。
“单价结合实体”是指能够特异性地且以单价结合模式与R/BBB结合的分子。本发明的血脑穿梭和/或缀合物的特征在于存在单价结合实体的单个单元,即本发明的血脑穿梭和/或缀合物包含单价结合实体的一个单元。所述单价结合实体包括但不限于蛋白、多肽、肽和抗体片段,包括Fab、Fab'、Fv片段、单链抗体分子例如单链Fab、scFv。所述单价结合实体可以是例如使用现有技术(如噬菌体展示或免疫接种)工程改造的支架蛋白。所述单价结合实体还可以是肽。在某些实施方案中,所述单价结合实体包含CH2-CH3 Ig结构域和针对血脑屏障受体的单Fab(sFab)。所述sFab通过接头偶联至CH2-CH3 Ig结构域的C-末端。在某些实施方案中,所述sFab是指转铁蛋白受体。
“单价结合模式”是指与R/BBB的特异性结合,其中单价结合实体和R/BBB之间的相互作用通过一个单独表位而发生。由于单个表位相互作用点,单价结合模式会阻止R/BBB的任何二聚化/多聚化。单价结合模式会阻止R/BBB的细胞内分选发生变化。
术语“表位”包括能够特异性结合抗体的任何多肽决定簇。在某些实施方案中,表位决定簇包括分子的化学活性表面分组(groupings),诸如氨基酸、糖侧链、磷酰基或磺酰基,且在某些实施方案中,可以具有特定的三维结构特征,和或特定的带电特性。表位是被抗体结合的抗原区域。
“转铁蛋白受体”(“TfR”)是一种跨膜糖蛋白(具有约180,000的分子量),其由参与脊椎动物中的铁摄取的两个二硫键键合的亚基(各自的表观分子量为约90,000)组成。在一个实施方案中,本文中的TfR是人TfR,其包含例如在Schneider等.Nature 311:675-678(1984)中的氨基酸序列。
本文中使用的“神经疾病”是指影响CNS和/或具有在CNS中的病因的疾病或病症。示例性的CNS疾病或病症包括、但不限于:神经病、淀粉样变性、癌症、眼的疾病或病症、病毒或微生物感染、炎症、缺血、神经变性疾病、癫痫发作、行为疾病和溶酶体贮积病。为了本申请的目的,将理解CNS包括眼,其通常通过血液-视网膜屏障与身体的其它部分隔离。神经疾病的具体例子包括、但不限于:神经变性疾病(包括、但不限于,雷维小体病(Lewy bodydisease),脊髓灰质炎后综合征(postpoliomyelitis syndrome),夏伊-德雷格综合征(Shy-Draeger syndrome),橄榄体脑桥小脑萎缩(olivopontocerebellar atrophy),帕金森病(帕金蛋白son's disease),多系统萎缩(multiple system atrophy),纹状体黑质变性(striatonigral degeneration),Tau病变(tauopathy)(包括、但不限于,阿尔茨海默病(Alzheimer disease)和核上性麻痹(supranuclear palsy)),朊病毒病(prion disease)(包括、但不限于,牛海绵状脑病(bovine spongiform encephalopathy),痒病(scrapie),克-雅综合征(Creutzfeldt-Jakob syndrome),库鲁病(kuru),格-施-沙病(Gerstmann-Straussler-Scheinker disease),慢性消耗性疾病(chronic wasting disease),和致命性家族性失眠症(fatal familial insomnia)),延髓性麻痹(bulbar palsy),运动神经元病(motor neuron disease),和heterodegenerative疾病(包括、但不限于卡纳范病(Canavan disease),亨廷顿病(Huntington's disease),神经元蜡样脂褐素沉积症(neuronal ceroid-lipofuscinosis),亚历山大病(Alexander's disease),图雷特综合征(Tourette's syndrome),门克斯扭结发综合征(Menkes kinky hair syndrome),科凯恩综合征(Cockayne syndrome),哈勒沃登-施帕茨综合征(Halervorden-Spatz syndrome),拉福拉病(lafora disease),雷特综合征(Rett syndrome),肝豆状核变性(hepatolenticular degeneration),莱施-奈恩综合征(Lesch-Nyhan syndrome),和翁-隆综合征(Unverricht-Lundborg syndrome)),痴呆(包括、但不限于,皮克病(Pick'sdisease),和脊髓小脑性共济失调(spinocerebellar ataxia)),癌症(例如CNS和/或脑的癌症,包括源自身体其它位置的癌症的脑转移灶)。
“神经疾病药物”是治疗一种或多种神经疾病的药物或治疗剂。本发明的神经疾病药物包括,但不限于,小分子化合物,抗体,肽,蛋白质,一种或多种CNS靶标的天然配体,一种或多种CNS靶标的天然配体的修饰形式,适体,抑制性核酸(即,小的抑制性RNA(siRNA)和短发夹RNA(shRNA)),核酶,和小分子,或上述中任何一种的活性片段。本发明的示例性神经疾病药物描述于此并且包括、但不限于:抗体,适体,蛋白质,肽,抑制性核酸和小分子和上述中任何一种的活性片段,它们是它们本身或特异性识别和/或作用于(即,抑制,活化,或检测)CNS抗原或靶标分子如,但不限于,淀粉样蛋白前体蛋白或其部分,淀粉样蛋白β,β-分泌酶,γ-分泌酶,tau,α-突触核蛋白,帕金蛋白,亨廷顿蛋白,DR6,早老蛋白,ApoE,神经胶质瘤或其它CNS癌症标志物,和神经营养因子。神经疾病药物的非限制性例子以及可以使用它们治疗的对应疾病:脑衍生的神经营养因子(BDNF),慢性脑损伤(神经发生),成纤维细胞生长因子2(FGF-2),抗-表皮生长因子受体脑癌,(EGFR)-抗体,神经胶质细胞系衍生的神经因子,帕金森病(GDNF),脑衍生的神经营养因子(BDNF),肌萎缩性侧索硬化,抑郁症,溶酶体酶,脑的溶酶体贮积疾病,睫状神经营养因子(CNTF),肌萎缩性侧索硬化,神经调节蛋白-1,精神分裂症,抗-HER2抗体(例如曲妥珠单抗),来自HER2-阳性癌症的脑转移。
“成像剂”是这样的化合物:其具有允许它的存在和/或位置被直接或间接检测到的一种或多种性质。这样的成像剂的例子包括蛋白和小分子化合物,其掺入使检测成为可能的标记实体。
“CNS抗原”或“脑靶标”是在CNS(包括脑)中表达的抗原和/或分子,其可以被抗体或小分子所靶向。这样的抗原和/或分子的例子包括、但不限于:β-分泌酶1(BACEl)、淀粉样蛋白β(Aβ)、表皮生长因子受体(EGFR)、人表皮生长因子受体2(HER2)、Tau、载脂蛋白E4(ApoE4)、α-突触核蛋白、CD20、亨廷顿蛋白、朊病毒蛋白(PrP)、富含亮氨酸的重复序列激酶2(LRRK2)、帕金蛋白、早老蛋白1、早老蛋白2、γ分泌酶、死亡受体6(DR6)、淀粉样蛋白前体蛋白(APP)、p75神经营养因子受体(p75NTR)和胱天蛋白酶6。在一个实施方案中,所述抗原是BACEl。
本文中的“天然序列”蛋白质是指包含在自然中发现的蛋白质的氨基酸序列的蛋白质,包括所述蛋白质的天然存在的变体。本文中使用的该术语包括从其天然来源分离的蛋白质或重组制备的蛋白质。
术语“抗体”在本文中以最宽的含义使用,并且具体地涵盖单克隆抗体、多克隆抗体、由至少两个完整抗体形成的多特异性抗体(例如、双特异性抗体)和抗体片段,只要它们表现出期望的生物活性即可。
“抗体片段”在本文中包括保持结合抗原的能力的完整抗体的一部分。抗体片段的例子包括Fab、Fab'、F(ab')2和Fv片段;双体;线性抗体;单链抗体分子例如单链Fab、scFv和由多个抗体片段形成的多特异性抗体。“单链Fab”形式例如描述在Hust M.等.BMCBiotechnol.2007年3月8日;7:14中。
本文中使用的术语“单克隆抗体”是指从一群基本上同质的抗体中获得的抗体,即除了可能的变体(该变体可以在产生单克隆抗体的过程中出现,此类变体通常少量存在)外,构成群体的个体抗体是相同的和/或结合相同的表位。相比于通常包括针对不同决定簇(表位)的不同抗体的多克隆抗体制备物,每个单克隆抗体针对抗原上的单一决定簇。除它们的特异性外,单克隆抗体的优势在于它们不受其它免疫球蛋白的污染。修饰语“单克隆”表明抗体从基本上同质的抗体群获得的特征,不应解释为要求通过任何特定方法来生产抗体。例如,根据本发明使用的单克隆抗体可通过最先由Kohler等,Nature,256:495(1975)描述的杂交瘤方法制备,或可以通过重组DNA方法(参见,例如,美国专利号4,816,567)制备。”单克隆抗体”也可以使用例如在Clackson等,Nature,352:624-628(1991)和Marks等,J.Mol.Biol.,222:581-597(1991)中所述的技术从噬菌体抗体文库分离。本文中的单克隆抗体的具体实例包括嵌合抗体、人源化抗体和人抗体,包括它们的抗原结合片段。单克隆抗体在本文中具体地包括:“嵌合”抗体(免疫球蛋白),其中重链和/或轻链的一部分与衍生自特定物种或属于特定抗体类别或亚类的抗体中的相应序列相同或同源,而所述链的剩余部分与衍生自另一物种或属于另一抗体类别或亚类的抗体中的相应序列相同或同源;以及此类抗体的片段,只要它们展现出期望的生物学活性(美国专利号4,816,567;Morrison等,Proc.Nat.Acad.Sci.USA(美国国家科学院学报)81:6851-6855(1984))。本文感兴趣的嵌合抗体包括“灵长类源化(primatized)”抗体,该抗体包含来源于非人灵长类动物(例如旧大陆猴(Old World Monkey),如狒狒、恒河猴(rhesus)或食蟹猴(cynomolgus monkey))的可变结构域抗原-结合序列以及人恒定区序列(美国专利号5,693,780)。
非人(例如鼠)抗体的“人源化”形式指最低限度包含衍生自非人免疫球蛋白的序列的嵌合抗体。在大部分情况中,人源化抗体是人免疫球蛋白(受体抗体),其中受体高变区的残基被具有所需特异性、亲和力和能力的非人物种(供体抗体)(诸如小鼠、大鼠、兔或非人灵长类动物)的高变区残基替换。在有些情况中,将人免疫球蛋白的框架区(FR)残基用相应的非人残基替换。此外,人源化抗体可包含在受体抗体中或在供体抗体中没有发现的残基。进行这些修饰以进一步改进抗体的性能。一般而言,人源化抗体将包含基本上全部的至少一个、典型地两个可变结构域,其中所有或基本上所有高变区对应于非人免疫球蛋白的高变区,且所有或基本上所有FR是人免疫球蛋白序列的那些,不同之处在于如上所述的FR置换。人源化抗体任选还将包含至少部分免疫球蛋白恒定区,所述免疫球蛋白恒定区典型地是人免疫球蛋白的恒定区。更多细节见例如Jones等,自然(Nature)321:522-525(1986);Riechmann等,自然(Nature)332:323-329(1988);及Presta,Curr.Op.Struct.Biol.2:593-596(1992)。
“人抗体”在本文中是包含这样的氨基酸序列结构的抗体,所述氨基酸序列结构与可获得自人B细胞的抗体的氨基酸序列结构对应,并且包括人抗体的抗原结合片段。可以通过多种技术鉴定或制备这样的抗体,所述技术包括、但不限于:通过在免疫后能够在不存在内源免疫球蛋白生产的情况下生产人抗体的转基因动物(例如,小鼠)生产(参见,例如,Jakobovits等,Proc.Natl.Acad.Sci.USA,90:2551(1993);Jakobovits等,Nature,362:255-258(1993);Bruggermann等,Year in Immuno.,7:33(1993);和美国专利号5,591,669,5,589,369和5,545,807));从表达人抗体或人抗体片段的噬菌体展示文库选择(参见,例如,McCafferty等,Nature 348:552-553(1990);Johnson等,Current Opinion inStructural Biology 3:564-571(1993);Clackson等,Nature,352:624-628(1991);Marks等,J.Mol.Biol.222:581-597(1991);Griffith等,EMBO J.12:725-734(1993);美国专利号5,565,332和5,573,905);通过体外活化的B细胞生成(参见美国专利5,567,610和5,229,275);和分离自生产人抗体的杂交瘤。
“多特异性抗体”在本文中是对至少两个不同的表位具有结合特异性的抗体。示例性多特异性抗体可以结合R/BBB和脑抗原两者。多特异性抗体可以被制备成全长抗体或抗体片段(例如F(ab')2双特异性抗体)。也预期有改造的具有两个、三个或更多个(例如四个)功能性抗原结合位点的抗体(参见,例如,美国申请号US 2002/0004587 A1,Miller等)。多特异性抗体可以被制备成全长抗体或抗体片段。
本文中的抗体包括具有改变的抗原结合或生物学活性的“氨基酸序列变体”。这样的氨基酸变化的例子包括具有增强的对抗原的亲和力的抗体(例如“亲和力成熟”抗体),和具有改变的Fc区(如果存在的话)的抗体,例如具有改变的(增加或减小的)依赖抗体的细胞介导的细胞毒性(ADCC)和/或依赖补体的细胞毒性(CDC)的抗体(参见,例如,WO 00/42072,Presta,L.和WO 99/51642,Iduosogie等);和/或具有增加的或减小的血清半衰期的抗体(参见,例如,WO00/42072,Presta,L.)。
“亲和力修饰的变体”具有一个或多个被置换的亲本抗体的高变区或框架残基(例如亲本嵌合、人源化或人抗体的),其改变(增加或减小)亲和力。在一个实施方案中,根据本发明,所得的被选用于进一步开发的变体将具有减小的对R/BBB的亲和力。产生这种置换变体的简便方式是使用噬菌体展示。简言之,将若干个高变区位点(例如6-7个位点)突变以在每个位点产生所有可能的氨基置换。因此产生的抗体变体以单价形式从丝状噬菌体颗粒展示为与包装在每个颗粒内的M13的基因III产物的融合体(fusion)。然后对噬菌体展示的变体的生物学活性(例如结合亲和力)进行筛选。为了鉴定用于修饰的候选高变区位点,可以进行丙氨酸扫描诱变以鉴别显著有助于抗原结合的高变区残基。可替换地,或另外地,可能有利的是分析抗原-抗体复合物的晶体结构从而鉴别抗体及其靶标间的接触点。根据本文所述的技术,这样的接触残基和邻近残基是置换的候选物。在这样的变体产生后,对一组变体进行筛选,并且可以选择具有改变的亲和力的抗体用于进一步的开发。
本文中的抗体可以是“糖基化变体”以使与Fc区相连的任何糖(如果存在的话)被改变。例如,具有缺乏与抗体的Fc区偶联的岩藻糖的成熟糖结构的抗体描述于美国专利申请号US 2003/0157108(Presta,L.)中。也参见US 2004/0093621(Kyowa Hakko Kogyo Co.,Ltd)。在与抗体的Fc区连接的糖中具有平分型N-乙酰葡糖胺(GlcNAc)的抗体引用在WO2003/011878(Jean-Mairet等)和美国专利号6,602,684(Umana等)中。在与抗体的Fc区连接的寡糖中具有至少一个半乳糖残基的抗体在WO 1997/30087,Patel等中被报道。也参见WO1998/58964(Raju,S.)和WO 1999/22764(Raju,S.),其涉及具有改变的与其Fc区连接的糖的抗体。也参见US 2005/0123546(Umana等),其描述了具有修饰的糖基化的抗体。术语“高变区”当在本文中使用时是指抗体的负责抗原结合的氨基酸残基。高变区包含来自“互补决定区”或“CDR”的氨基酸残基(例如轻链可变结构域中的残基24-34(L1)、50-56(L2)和89-97(L3)和重链可变结构域中的31-35(H1)、50-65(H2)和95-102(H3);Kabat等,免疫学感兴趣的蛋白的序列(Sequences of Proteins of Immunological Interest),第5版.公众健康服务(Public Health Service),国立卫生研究所(National Institutes of Health),Bethesda,MD.(1991))和/或来自“高变环”的那些残基(例如轻链可变结构域中的残基26-32(L1)、50-52(L2)和91-96(L3)以及重链可变结构域中的26-32(H1)、53-55(H2)和96-101(H3);Chothia和Lesk,分子生物学杂志(J.Mol.Biol.)196:901-917(1987))。”框架”或”FR”残基是不同于本文所定义的高变区残基的那些可变结构域残基。
“全长抗体”是这样的抗体,其包含抗原-结合可变区以及轻链恒定结构域(CL)和重链恒定结构域,CH1,CH2和CH3。恒定结构域可以是天然序列恒定结构域(例如人天然序列恒定结构域)或其氨基酸序列变体。
“裸抗体”是没有缀合异源分子(如细胞毒性实体、聚合物或放射性标记)的抗体(如本文所定义的)。
抗体“效应子功能”指那些可归因于抗体的Fc区(天然序列Fc区或氨基酸序列变体Fc区)的生物学活性。抗体效应子功能的例子包括:C1q结合,补体依赖性细胞毒性(CDC),Fc受体结合,抗体依赖性细胞介导的细胞毒性(ADCC)等。在一个实施方案中,本文中的抗体基本上缺少效应子功能。
术语“抗体依赖性的细胞的细胞毒性(ADCC)”是指在有效应细胞存在下抗体对人靶细胞的裂解。术语“补体依赖性的细胞毒性(CDC)”指由补体因子C1q与大多数IgG抗体亚类的Fc部分结合而起始的过程。C1q与抗体的结合由在所谓的结合位点的定义的蛋白-蛋白相互作用所导致。这样的Fc部分结合位点是现有技术中已知的。这些Fc部分结合位点例如特征在于氨基酸L234、L235、D270、N297、E318、K320、K322、P331和P329(根据Kabat的EU索引编号)。亚类IgG1、IgG2和IgG3的抗体通常显示包括C1q和C3结合的补体激活,而IgG4不激活补体系统并且不结合C1q和/或C3。
取决于其重链恒定结构域的氨基酸序列,可以将全长抗体分配到不同的”类别”。有五个主要类别的全长抗体:IgA、IgD、IgE、IgG和IgM,并且这些中的数个可以进一步被划分为“亚类”(同种型),例如,IgGl、IgG2、IgG3、IgG4、IgA和IgA2。对应于不同类别的抗体的重链恒定结构域分别被称为α、δ、ε、γ和μ。不同类别的免疫球蛋白的亚基结构和三维构型是已知的。术语”重组抗体”,当在本文中使用时,是指这样的抗体(例如嵌合、人源化或人抗体或其抗原结合片段),该抗体由包含编码所述抗体的核酸的重组宿主细胞表达。用于生产重组抗体的“宿主细胞”的例子包括:(1)哺乳动物细胞,例如,中国仓鼠卵巢(CHO)、COS、骨髓瘤细胞(包括Y0和NS0细胞),幼仓鼠肾细胞(BHK),Hela细胞和Vero细胞;(2)昆虫细胞,例如,sf9,sf21和Tn5;(3)植物细胞,例如属于烟草属(genus Nicotiana)的植物(例如烟草(Nicotiana tabacum));(4)酵母细胞,例如,属于酵母属(genus Saccharomyces)的那些(例如酿酒酵母(Saccharomyces cerevisiae))或属于曲霉属(genus Aspergillus)的那些(例如黑曲霉(Aspergillus niger));(5)细菌细胞,例如大肠杆菌(Escherichia.coli)细胞或枯草芽孢杆菌(Bacillus subtilis)细胞等。
本文中使用的“特异性结合”或“特异地结合”是指抗体选择性地或优先地结合抗原。通常使用标准测定,如斯卡查德分析或表面等离子共振技术(例如使用)确定结合亲和力。
与参照抗体“结合相同表位的抗体”是指这样的抗体,其在竞争测定中阻断50%以上的所述参照抗体与其抗原的结合,反之,参照抗体在竞争测定中阻断50%以上的该抗体与其抗原的结合。
术语“细胞毒性剂”用在本发明中指抑制或防止细胞功能和/或引起细胞死亡或破坏的物质。细胞毒性剂包括、但不限于:放射性同位素(例如,At211,1131,1125,Y90,Re186,Re188,Sm153,Bi212,P32,Pb212和Lu的放射性同位素);化疗剂或药物(例如,甲氨蝶呤(methotrexate),阿霉素(adriamicin),长春花生物碱(vinca alkaloids)(长春新碱(vincristine),长春碱(vinblastine),依托泊苷(etoposide)),多柔比星(doxorubicin),美法仑(melphalan),丝裂霉素(mitomycin)C,苯丁酸氮芥(chlorambucil),柔红霉素(daunorubicin)或其它嵌入剂);生长抑制剂;酶及其片段如核酸水解酶;抗生素;毒素如小分子毒素或细菌、真菌、植物或动物起源的酶促活性毒素,包括其片段和/或变体。
试剂例如药物制剂的”有效量”是指在需要的剂量和时间阶段有效获得所需的治疗或预防结果的量。
术语“Fc区”在本文中用于定义免疫球蛋白重链的C端区域,所述区域包含恒定区的至少一部分。Fc区包含免疫球蛋白的CH2和CH3结构域。该术语包括天然序列Fc区和变体Fc区。在一个实施方案中,人IgG重链Fc区从Cys226或Pro230延伸至重链的羧基端。但是,Fc区的C端赖氨酸(Lys447)可以存在或可以不存在。除非另外说明,Fc区或恒定区中的氨基酸残基的编号是根据EU编号系统,其也被称为EU索引,如在Kabat等,Sequences of Proteinsof Immunological Interest(免疫学感兴趣的蛋白质的序列),第5版.Public HealthService,National Institutes of Health,Bethesda,MD,1991中所述。“框架”或”FR”是指除高变区(HVR)残基之外的可变结构域残基。可变结构域的FR通常由以下四个FR结构域组成:FR1,FR2,FR3和FR4。因此,HVR和FR序列通常以下列顺序出现在VH(或VL)中:FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4。
本文中使用的术语“CH2-CH3 Ig实体”是指从免疫球蛋白CH2或CH3结构域衍生出的蛋白实体。“CH2-CH3 Ig实体”包含2个形成二聚体的“CH2-CH3”多肽。所述免疫球蛋白可以是IgG、IgA、IgD、IgE或IgM。在一个实施方案中,所述CH2-CH3 Ig实体衍生自IgG免疫球蛋白,且在本文中被称作“CH2-CH3 IgG实体”。该术语包括CH2-CH3结构域的天然序列和变体CH2-CH3结构域。在一个实施方案中,所述“CH2-CH3 Ig实体”衍生自人重链CH2-CH3 IgG结构域,所述结构域从Cys226或从Pro230延伸至重链的羧基端。但是,Fc区的C-端赖氨酸(Lys447)可以存在或可以不存在。除非在本文中另外说明,CH2-CH3结构域区域或恒定区中的氨基酸残基的编号是根据EU编号系统,其也被称为EU索引,如在Kabat等,Sequences ofProteins of Immunological Interest(免疫学感兴趣的蛋白质的序列),第5版.PublicHealth Service,National Institutes of Health,Bethesda,MD,1991中所述。
“缀合物”是与一个或多个异源分子缀合的本发明的融合蛋白,所述异源分子包括、但不限于标记、神经疾病药物或细胞毒性剂。
本文中使用的“接头”是指化学接头或单链肽接头,其将血脑屏障穿梭体和/或融合蛋白和/或本发明的缀合物的不同实体共价地连接。例如,所述接头将脑效应物实体与单价结合实体连接。例如,如果单价结合实体包含CH2-CH3 Ig实体和针对血脑屏障受体的sFab,那么所述接头将sFab与CH3-CH2 Ig实体的C-末端连接。将脑效应物实体与单价结合实体连接的接头(第一接头)和将sFab与CH2-CH3 Ig结构域的C-末端连接的接头(第二接头)可以相同或不同。
可以使用单链肽接头,其包含1-20个通过肽键连接的氨基酸。在某些实施方案中,所述氨基酸选自2种天然存在的氨基酸。在某些其它实施方案中,所述氨基酸中的一个或多个选自甘氨酸、丙氨酸、脯氨酸、天冬酰胺、谷氨酰胺和赖氨酸。在其它实施方案中,所述接头是化学接头。在某些实施方案中,所述接头是具有至少25个氨基酸长度的氨基酸序列的单链肽,优选地具有32-50个氨基酸的长度。在一个实施方案中,所述接头是(GxS)n,其中G=甘氨酸,S=丝氨酸(x=3、n=8、9或10且m=0、1、2或3)或(x=4和n=6、7或8且m=0、1、2或3),优选地,其中x=4,n=6或7且m=0、1、2或3,更优选地,其中x=4,n=7且m=2。在一个实施方案中,所述接头是(G4S)4(Seq.Id.No.17)。在一个实施方案中,所述接头是(G4S)6G2(Seq.Id.No.13)。
可以使用多种化学接头进行缀合。例如,使用多种双功能的蛋白偶联剂诸如N-琥珀酰亚胺基-3-(2-吡啶基二硫)丙酸酯(SPDP)、琥珀酰亚胺基-4-(N-马来酰亚胺基甲基)环己烷-l-甲酸酯(SMCC)、亚氨基硫杂环戊烷(IT)、亚胺酯的双功能衍生物(诸如己二亚氨酸二甲酯HC1)、活性酯(诸如辛二酸二琥珀酰亚胺酯)、醛(诸如戊二醛)、二-叠氮基化合物(诸如双(对叠氮基苯甲酰基)己烷二胺)、二-重氮鎓衍生物(诸如二-(对重氮鎓苯甲酰基)-乙二胺)、二异氰酸酯(诸如甲苯2,6-二异氰酸酯)和双活性的氟化合物(诸如l,5-二氟-2,4-二硝基苯),可以缀合单价结合实体或融合蛋白和脑效应物实体。所述接头可以是“可切割的接头”,从而促进效应物实体在递送至脑以后的释放。例如,可以使用酸不稳定的接头、肽酶敏感的接头、光不稳定的接头、二甲基接头或含有二硫键的接头(Chari等,CancerRes.52:127-131(1992);美国专利号5,208,020)。
共价缀合可以直接进行或通过接头进行。在某些实施方案中,直接缀合通过构建蛋白融合体进行(即,通过编码针对R/BBB的单价结合实体和效应物实体的两种基因的基因融合并且表达为单一蛋白)。在某些实施方案中,直接缀合通过在针对R/BBB的单价结合实体的两部分之一上的反应基团与脑效应物实体上的对应基团或接受体之间形成共价键进行。在某些实施方案中,直接缀合通过将要缀合的两种分子中的一种进行修饰(即基因修饰)而进行,从而包括在适当条件下形成与要缀合的其它分子的共价连接的反应基团(作为非限制性例子,巯基或羧基)。作为一个非限制性例子,可以引入具有期望的反应基团(即,半胱氨酸残基)的分子(即,氨基酸),例如,引入到针对R/BBB抗体的单价结合实体中,并且与神经药物形成二硫键。使核酸与蛋白共价缀合的方法也是本领域已知的(即,光交联,参见,例如,Zatsepin等.Russ.Chem.Rev.(俄罗斯化学综述)74:77-95(2005))。还可以使用多种接头进行缀合。例如,使用多种双功能的蛋白偶联剂诸如N-琥珀酰亚胺基-3-(2-吡啶基二硫)丙酸酯(SPDP)、琥珀酰亚胺基-4-(N-马来酰亚胺基甲基)环己烷-l-甲酸酯(SMCC)、亚氨基硫杂环戊烷(IT)、亚胺酯的双功能衍生物(诸如己二亚氨酸二甲酯HC1)、活性酯(诸如辛二酸二琥珀酰亚胺酯)、醛(诸如戊二醛)、二-叠氮基化合物(诸如双(对叠氮基苯甲酰基)己烷二胺)、二-重氮鎓衍生物(诸如二-(对重氮鎓苯甲酰基)-乙二胺)、二异氰酸酯(诸如甲苯2,6-二异氰酸酯)和双活性的氟化合物(诸如l,5-二氟-2,4-二硝基苯),可以缀合单价结合实体和效应物实体。也可以使用包含通过肽键连接的1-20个氨基酸的肽接头。在某些这样的实施方案中,氨基酸选自20种天然存在的氨基酸。在某些其它这样的实施方案中,一个或多个氨基酸选自甘氨酸、丙氨酸、脯氨酸、天冬酰胺、谷氨酰胺和赖氨酸。接头可以是“可切割的接头”,从而促进效应物实体在递送至脑后的释放。例如,可以使用酸不稳定的接头、肽酶敏感的接头、光不稳定的接头、二甲基接头或含有二硫键的接头(Chari等,CancerRes.52:127-131(1992);美国专利号5,208,020)。
“标记”是与本文中的融合蛋白偶联并被用于检测或成像的标志物。这样的标记的例子包括:放射性标记、荧光团、生色团或亲和标签。在一个实施方案中,标记是用于医疗成像的放射性标记,例如tc99m或I123,或用于核磁共振(NMR)成像(也被称为磁共振成像,mri)的自旋标记,如又有碘-123,碘-131,铟-111,氟-19,碳-13,氮-15,氧-17,钆,锰,铁等。“个体”或“受试者”是哺乳动物。哺乳动物包括、但不限于,家养动物(例如,牛,羊,猫,狗和马),灵长类动物(例如,人和非人灵长类动物如猴),兔,以及啮齿类动物(例如,小鼠和大鼠)。在某些实施方案中,个体或受试者是人。
“分离的”抗体是这样的抗体,其已经与其天然环境的组分分离。在某些实施方案中,将抗体纯化至超过95%或99%纯度,如通过例如电泳(例如,SDS-PAGE,等电聚焦(IEF),毛细管电泳)或层析(例如,离子交换或反相HPLC)确定的。对于用于评估抗体纯度的方法的综述,参见,例如,Flatman等,J.Chromatogr.B 848:79-87(2007)。
术语“包装说明书”用于指常规地包含在治疗性产品的商业包装中的说明书,其含有关于适应症、用法、剂量、施用、组合疗法、禁忌症和/或关于使用此类治疗性产品的警告的信息。
术语“药物制剂”指这样的制剂,其以允许包含在其中的活性成分的生物学活性有效的形式存在,并且不包含对被施用所述制剂的受试者具有不可接受的毒性的另外的成分。
“药用载体”是指药物制剂中不同于活性成分的成分,其对受试者是无毒的。药用载体包括、但不限于缓冲剂、赋形剂、稳定剂或防腐剂。
本文中使用的“治疗(treatment)”(及其语法变化如“治疗(treat)”或“治疗(treating)”)指在尝试改变待治疗的个体的天然进程中的临床干预,并且可以为了预防或在临床病理学的进程中进行。治疗的理想效果包括、但不限于防止疾病发生或复发,缓和征状,消除疾病的任何直接或间接病理学后果,预防转移,降低疾病进展速率,改善或减轻疾病状态,和征状缓解或改善的预后。在某些实施方案中,将本发明的抗体用于延缓疾病的发生或减缓疾病的进展。
组合物和方法
本发明的方法和制品使用,或包括,结合R/BBB的血脑屏障穿梭体和/或融合蛋白。要用于生产或筛选单价结合实体的R/BBB抗原可以是,例如,包含所需表位的可溶形式的或其部分(例如胞外结构域)。可替换地,或另外地,在其细胞表面表达BBB-R的细胞可以用于产生或筛选单价结合实体。可用于生产单价结合实体的R/BBB的其它形式对于本领域技术人员将是明显的。本文中的R/BBB的例子包括转铁蛋白受体(TfR)、胰岛素受体、胰岛素样生长因子受体(IGF-R)、低密度脂蛋白受体相关的蛋白1(LRP1)和LRP8和结合肝素的表皮生长因子样生长因子(HB-EGF)。
根据本发明,选择针对R/BBB的“单价结合”实体(例如针对TfR的单价结合实体),这基于本文中证实此种单价结合实体显示提高的CNS(例如,脑)摄取的数据。为了鉴别此种结合实体,用于测量单价结合模式的多种测定是可用的,其包括、但不限于:Scatchard测定和表面等离子体共振技术(例如使用)和本文描述的体内研究。
因而,本发明提供了制备可用于将脑效应物实体(例如神经疾病药物)运输穿过血脑屏障的单价结合实体的方法,所述方法包括:从针对R/BBB的单价结合部分集合中选择单价结合实体,因为它具有对R/BBB的单价结合模式。所述单价结合模式确保某些R/BBB的有效BBB穿过,但是不会干扰受体正常细胞内筛选。
对于神经病疾病,可以选择作为镇痛药的神经药物,包括、但不限于,麻醉药/阿片类镇痛药(即,吗啡,芬太尼(fentanyl),丙碘酮(hydrocodone),哌替啶(meperidine),美沙酮(methadone),羟吗啡酮(oxymorphone),喷他佐辛(pentazocine),丙氧芬(propoxyphene),曲马朵(tramadol),可待因(codeine)和羟可酮(oxycodone)),非甾类抗炎药(NSAID)(即,布洛芬(ibuprofen),萘普生(naproxen),双氯芬酸(diclofenac),二氟尼柳(diflunisal),依托度酸(etodolac),非诺洛芬(fenoprofen),氟比洛芬(flurbiprofen),吲哚美辛(indomethacin),酮咯酸(ketorolac),甲芬那酸(mefenamicacid),美洛昔康(meloxicam),萘丁美酮(nabumetone),奥沙普秦(oxaprozin),吡罗昔康(piroxicam),舒林酸(sulindac)和托美丁(tolmetin)),皮质类甾醇(即,可的松(cortisone),泼尼松(prednisone),泼尼松龙(prednisolone),地塞米松(dexamethasone),甲泼尼龙(methylprednisolone)和去炎松(triamcinolone)),抗偏头痛剂(即,sumatriptin,阿莫曲普坦(almotriptan),夫罗曲普坦(frovatriptan),舒马普坦(sumatriptan),利扎曲普坦(rizatriptan),依来曲普坦(eletriptan),佐米曲普坦(zolmitriptan),双氢麦角胺(dihydroergotamine),依来曲普坦(eletriptan)和麦角胺(ergotamine)),醋氨酚(acetaminophen),水杨酸盐(即,阿司匹林(aspirin),水杨酸胆碱(choline salicylate),水杨酸镁(magnesium salicylate),二氟尼柳(diflunisal)和双水杨酯(salsalate)),抗惊厥药(即,卡马西平(carbamazepine),氯硝西泮(clonazepam),加巴喷丁(gabapentin),拉莫三嗪(lamotrigine),普瑞巴林(pregabalin),噻加宾(tiagabine)和托吡酯(topiramate)),麻醉药(即,异氟醚(isoflurane),三氯乙烯(trichloroethylene),氟烷(halothane),七氟烷(sevoflurane),苯佐卡因(benzocaine),氯普鲁卡因(chloroprocaine),可卡因(cocaine),环美卡因(cyclomethycaine),二甲卡因(dimethocaine),丙氧卡因(propoxycaine),普鲁卡因(procaine),奴佛卡因(novocaine),丙美卡因(proparacaine),丁卡因(tetracaine),阿替卡因(articaine),布比卡因(bupivacaine),卡替卡因(carticaine),辛可卡因(cinchocaine),依替卡因(etidocaine),左布比卡因(levobupivacaine),利多卡因(lidocaine),甲哌卡因(mepivacaine),哌罗卡因(piperocaine),丙胺卡因(prilocaine),罗哌卡因(ropivacaine),三甲卡因(trimecaine),蛤蚌毒素(saxitoxin)和河豚毒素(tetrodotoxin)),和cox-2-抑制剂(即,塞来昔布(celecoxib),罗非昔布(rofecoxib)和伐地考昔(valdecoxib))。对于伴有眩晕的神经疾病,可以选择作为抗眩晕剂的神经药物,其包括、但不限于,美克洛嗪(meclizine),苯海拉明(diphenhydramine),异丙嗪(promethazine)和地西泮(diazepam)。对于伴有恶心的神经疾病,可以选择作为抗恶心剂的神经药物,其包括、但不限于,异丙嗪(promethazine),氯丙嗪(chlorpromazine),丙氯拉嗪(prochlorperazine),曲美苄胺(trimethobenzamide)和甲氧氯普胺(metoclopramide)。对于神经变性疾病,可以选择是生长激素或神经营养因子的神经药物;实例包括、但不限于脑源性神经营养因子(BDNF),神经生长因子(NGF),神经营养因子-4/5,成纤维细胞生长因子(FGF)-2和其它FGF,神经营养因子(NT)-3,促红细胞生成素(EPO),肝细胞生长因子(HGF),表皮生长因子(EGF),转化生长因子(TGF)-α,TGF-β,血管内皮生长因子(VEGF),白介素-1受体拮抗剂(IL-1ra),睫状神经营养因子(CNTF),神经胶质源性神经营养因子(GDNF),neurturin,血小板源性生长因子(PDGF),调蛋白(heregulin),神经调节蛋白,artemin,persephin,白介素,胶质细胞源性神经营养因子(GFR),粒细胞集落刺激因子(CSF),粒细胞-巨噬细胞-CSF,导蛋白(netrin),心肌营养蛋白-1,刺猬分子(hedgehogs),白血病抑制因子(LIF),中期因子,多效营养因子,骨形成蛋白(BMP),导蛋白,皂化蛋白,脑信号蛋白和干细胞因子(SCF)。对于癌症,可以选择是化疗剂的神经药物。化疗剂的例子包括烷基化试剂,如塞替哌(thiotepa)和环磷酰胺(cyclosphosphamide)烷基磺酸酯(alkyl sulfonates)如白消安(busulfan),英丙舒凡(improsulfan)和哌泊舒凡(piposulfan);吖丙啶类(aziridines)如苯佐替派(benzodopa)、卡波醌(carboquone)、美妥替哌(meturedopa)和乌瑞替哌(uredopa);乙撑亚胺类(ethylenimines)和甲基蜜胺类(methylamelamines),包括六甲蜜胺(altretamine)、曲他胺(triethylenemelamine)、三亚乙基磷酰胺(triethylenephosphoramide)、三乙烯硫代磷酸胺(triethylenethiophosphoramide)和三羟甲蜜胺(trimethylomelamine);聚乙酸类(acetogenins)(特别是布拉他辛(bullatacin)和布拉他辛酮(bullatacinone));△-9-四氢大麻酚(delta-9-tetrahydrocannabinol)(屈大麻酚(dronabinol)、);β-拉帕醌(beta-lapachone);拉帕醇(lapachol);秋水仙碱(colchicines);桦木酸(betulinic acid);喜树碱(camptothecin)(包括合成的类似物托泊替康(topotecan)CPT-11(伊立替康(irinotecan))、乙酰喜树碱(acetylcamptothecin)、东莨菪亭(scopolectin)和9-氨基喜树碱(9-aminocamptothecin));苔藓抑素(bryostatin);海绵多烯酮类化合物(callystatin);CC-1065(包括其阿多来新(adozelesin)、卡折来新(carzelesin)和比折来新(bizelesin)合成类似物);鬼臼毒素(podophyllotoxin);鬼臼酸(podophyllinic acid);替尼泊苷(teniposide);隐藻素类(cryptophycins)(特别是隐藻素1和隐藻素8);多拉司他汀(dolastatin);倍癌霉素(duocarmycin)(包括合成的类似物、KW-2189和CB1-TM1);艾榴素(eleutherobin);水鬼蕉碱(pancratistatin);匍枝珊瑚醇(sarcodictyin);海绵素(spongistatin);氮芥(nitrogen mustards)如苯丁酸氮芥(chlorambucil)、萘氮芥(chlornaphazine)、胆磷酰胺(chlorophosphamide)、雌莫司汀(estramustine)、异环磷酰胺(ifosfamide)、氮芥(mechlorethamine)、盐酸氧氮芥(mechlorethamine oxidehydrochloride)、美法仑(melphalan)、新氮芥(novembichin)、苯芥胆甾醇(phenesterine)、泼尼莫司汀(prednimustine)、曲磷胺(trofosfamide)、尿嘧啶氮芥(uracil mustard);亚硝基脲类(nitrosoureas)如卡莫司汀(carmustine)、氯脲菌素(chlorozotocin)、福莫司汀(fotemustine)、洛莫司汀(lomustine)、尼莫司汀(nimustine)和雷莫司汀(ranimnustine);抗生素如烯二炔类(enediyne)抗生素(例如加利车霉素(calicheamicin),尤其是加利车霉素γ1I和加利车霉素ωI1(参见例如Agnew,Chem.Intl.Ed.Engl.,33:183-186(1994));烯二炔蒽环类抗生素(dynemicin),包括烯二炔蒽环类抗生素A;埃斯波霉素(esperamicin);以及新制癌菌素(neocarzinostatin)生色团和相关色素蛋白烯二炔类抗生素生色团)、阿克拉霉素(aclacinomysins)、放线菌素(actinomycin)、蒽霉素(authramycin)、偶氮丝氨酸(azaserine)、博来霉素(bleomycins)、放线菌素C(cactinomycin)、carabicin、洋红霉素(carminomycin)、嗜癌霉素(carzinophilin)、色霉素(chromomycins)、放线菌素D(dactinomycin)、柔红霉素(daunorubicin)、地托比星(detorubicin)、6-重氮-5-氧代-L-正亮氨酸(6-diazo-5-oxo-L-norleucine)、多柔比星(doxorubicin)(包括吗啉代-多柔比星(morpholino-doxorubicin)、氰基吗啉代-多柔比星(cyanomorpholino-doxorubicin)、2-吡咯啉-多柔比星(2-pyrrolino-doxorubicin)和脱氧多柔比星(deoxydoxorubicin))、表柔比星(epirubicin)、依索比星(esorubicin)、伊达比星(idarubicin)、马塞罗霉素(marcellomycin)、丝裂霉素类(mitomycins)如丝裂霉素C、麦考酚酸(mycophenolicacid)、诺拉霉素(nogalamycin)、橄榄霉素(olivomycins)、培洛霉素(peplomycin)、紫菜霉素(porfiromycin)、嘌呤霉素(puromycin)、三铁阿霉素(quelamycin)、罗多比星(rodorubicin)、链黑霉素(streptonigrin)、链佐星(streptozocin)、杀结核菌素(tubercidin)、乌苯美司(ubenimex)、净司他丁(zinostatin)、佐柔比星(zorubicin);抗代谢物如甲氨喋呤(methotrexate)和5-氟尿嘧啶(5-fluorouracil)(5-FU);叶酸类似物如二甲叶酸(denopterin)、甲氨喋呤、喋罗呤(pteropterin)、三甲曲沙(trimetrexate);嘌呤类似物如氟达拉滨(fludarabine)、6-巯嘌呤(6-mercaptopurine)、硫咪嘌呤(thiamiprine)、硫鸟嘌呤(thioguanine);嘧啶类似物如安西他滨(ancitabine)、阿扎胞苷(azacitidine)、6-氮尿苷(6-azauridine)、卡莫氟(carmofur)、阿糖胞苷(cytarabine)、双脱氧尿苷(dideoxyuridine)、去氧氟尿苷(doxifluridine)、依诺他滨(enocitabine)、氟尿苷(floxuridine);雄激素类,诸如卡鲁睾酮(calusterone)、丙酸屈他雄酮(dromostanolonepropionate)、环硫雄醇(epitiostanol)、美雄烷(mepitiostane)、睾内酯(testolactone);抗肾上腺药(anti-adrenals)如氨鲁米特(aminoglutethimide)、米托坦(mitotane)、曲洛司坦(trilostane);叶酸补偿剂如亚叶酸(frolinic acid);醋葡醛内酯(aceglatone);羟醛磷酰胺配糖(aldophosphamide glycoside);5-氨基酮戊酸(aminolevulinic acid);恩尿嘧啶(eniluracil);安吖啶(amsacrine);bestrabucil;比生群(bisantrene);依达曲沙(edatraxate);defofamine;秋水仙胺(demecolcine);地吖醌(diaziquone);elfornithine;依利醋铵(elliptinium acetate);埃坡霉素(epothilone);依托格鲁(etoglucid);硝酸镓(gallium nitrate);羟基脲(hydroxyurea);香菇多糖(lentinan);氯尼达明(lonidainine);美登木素生物碱类(maytansinoids)如美登素(maytansine)和安丝菌素(ansamitocins);米托胍腙(mitoguazone);米托蒽醌(mitoxantrone);莫哌达醇(mopidanmol);尼曲吖啶(nitraerine);喷司他丁(pentostatin);异丙嗪(phenamet);吡柔比星(pirarubicin);洛索蒽醌(losoxantrone);2-乙基酰肼(2-ethylhydrazide);丙卡巴肼(procarbazine);多糖复合物(JHS Natural Products(JHS天然产品),Eugene,OR);雷佐生(razoxane);利索新(rhizoxin);西佐喃(sizofiran);锗螺胺(spirogermanium);细交链孢菌酮酸(tenuazonic acid);三亚胺醌(triaziquone);2,2’,2’-三氯三乙胺(2,2’,2”-trichlorotriethylamine);单端孢霉烯族化合物(trichothecenes)(特别是T-2毒素、verracurin A、杆孢菌素A(roridin A)和蛇形菌素(anguidine));乌拉坦(urethan);长春地辛(vindesine)达卡巴嗪(dacarbazine);甘露莫司汀(mannomustine);二溴甘露醇(mitobronitol);二溴卫矛醇(mitolactol);哌泊溴烷(pipobroman);gacytosine;阿糖胞苷(arabinoside)(“Ara-C”);塞替哌(thiotepa);紫杉烷类化合物(taxoid),例如紫杉醇(paclitaxel)(Bristol-Myers Squibb Oncology,Princeton,N.J.)、不含Cremophor的ABRAXANETM(ABRAXANETM Cremophor-free),紫杉醇的白蛋白改造的纳米颗粒制剂(American Pharmaceutical Partners,Schaumberg,Illinois)和多西他塞(docetaxel)(-Poulenc Rorer,Antony,法国));苯丁酸氮芥(chloranbucil);吉西他滨(gemcitabine)6-硫鸟嘌呤(6-thioguanine);巯嘌呤(mercaptopurine);甲氨喋呤;铂类似物如顺铂(cisplatin)和卡铂(carboplatin);长春碱(vinblastine)铂;依托泊苷(etoposide)(VP-16);异环磷酰胺(ifosfamide);米托蒽醌(mitoxantrone);长春新碱(vincristine)奥沙利铂(oxaliplatin);亚叶酸(leucovorin);长春瑞滨(vinorelbine)诺安托(novantrone);依达曲沙(edatrexate);道诺霉素(daunomycin);氨基喋呤(aminopterin);伊班膦酸盐(ibandronate);拓扑异构酶抑制剂RFS 2000;二氟甲基鸟氨酸(difluoromethylornithine)(DMFO);类视黄酸类(retinoids)如视黄酸(retinoic acid);卡培他滨(capecitabine)以上任何一种的药用盐、酸或衍生物;以及以上各项中的两个以上的组合,CHOP,即环磷酰胺、多柔比星、长春新碱、和泼尼松龙(prednisolone)的组合疗法的缩写;以及FOLFOX,即与5-FU和亚叶酸(leucovorin)组合的奥沙利铂(oxaliplatin)(ELOXATINTM)的治疗方案的缩写。
同样包括在对化疗剂的该定义中的是抗激素剂,其作用为调节、降低、阻断或抑制可促进癌生长的激素效果,并且通常为系统或全身治疗的形式。它们自身可以是激素。实例包括抗雌激素类和选择性雌激素受体调控物类(SERM),包括,例如,他莫昔芬(tamoxifen)(包括他莫昔芬),雷洛昔芬(raloxifene),屈洛昔芬(droloxifene),4-羟基他莫西芬,曲沃昔芬(trioxifene),keoxifene,LY117018,奥那司酮(onapristone),和托瑞米芬(toremifene));抗黄体酮;雌激素受体下调剂(ERDs);起作用抑制或关闭卵巢的药剂,例如,促黄体生成激素释放素(leutinizinghormone-releasing hormone)(LHRH)激动剂如和醋酸亮丙立德(leuprolide acetate),醋酸戈舍瑞林(goserelin acetate)、醋酸布舍瑞林(buserelinacetate)和tripterelin;其它抗雄激素类,如氟他胺(flutamide)、尼鲁米特(nilutamide)和比卡鲁胺(bicalutamide);和抑制芳香酶的芳香酶抑制剂,其调节肾上腺中的雌激素生产,诸如例如,4(5)-咪唑、氨鲁米特(aminoglutethimide)、醋酸甲地孕酮(megestrol acetate)、依西美坦(exemestane)、福美坦(formestanie),法倔唑(fadrozole)、伏氯唑(vorozole)、来曲唑(letrozole)和阿那曲唑(anastrozole)。此外,对化疗剂的这种定义包括二膦酸盐类(bisphosphonates)如氯膦酸盐(clodronate)(例如,或)、依替膦酸盐(etidronate)、NE-58095、唑来膦酸(zoledronicacid)/唑来膦酸盐(zoledronate)、阿仑膦酸盐(alendronate)、帕米膦酸盐(pamidronate)、替鲁膦酸盐(tiludronate)或利塞膦酸盐(risedronate);以及曲沙他滨(troxacitabine)(1,3-二氧戊环核苷胞嘧啶类似物);反义寡核苷酸,特别是抑制在涉及异常细胞增殖的信号传导途径中基因的表达的那些,诸如例如,PKC-α、Raf、H-Ras和表皮生长因子受体(EGF-R);疫苗诸如疫苗和基因治疗疫苗、例如,疫苗、疫苗和疫苗;拓扑异构酶1抑制剂;rmRH;托西拉帕替尼(lapatinib ditosylate)(ErbB-2和EGFR双重酪氨酸激酶小分子抑制剂,也已知为GW572016);和以上任何一种的药用盐、酸或衍生物。
可以被选作用于癌症治疗或预防的神经药物的另一组化合物是抗癌症免疫球蛋白(包括、但不限于,曲妥珠单抗(trastuzumab),贝伐珠单抗(bevacizumab),阿仑单抗(alemtuxumab),西妥昔单抗(cetuximab),吉妥珠单抗(gemtuzumab ozogamicin),替尼莫单抗(ibritumomab tiuxetan),帕尼单抗(panitumumab)和利妥昔单抗(rituximab))。在一些情况中,与有毒的标记结合的抗体可以用于靶向并杀死目的细胞(即,癌症细胞),所述抗体包括、但不限于,具有放射性标记的托西莫单抗(tositumomab)。
对于眼疾病或病症,可以选择是以下各项的神经药物:抗新生血管眼科试剂(即,贝伐珠单抗(bevacizumab),兰尼单抗(ranibizumab)和培加尼布(pegaptanib)),眼科青光眼药(即,卡巴胆碱(carbachol),肾上腺素(epinephrine),地美溴铵(demecariumbromide),阿可乐定(apraclonidine),溴莫尼定(brimonidine),布林唑胺(brinzolamide),左布诺洛尔(levobunolol),噻吗洛尔(timolol),倍他洛尔(betaxolol),多佐胺(dorzolamide),比马前列素(bimatoprost),卡替洛尔(carteolol),美替洛尔(metipranolol),地匹福林(dipivefrin),曲伏前列素(travoprost)和拉坦前列素(latanoprost)),碳酸酐酶抑制剂(即,醋甲唑胺(methazolamide)和乙酰唑胺(acetazolamide)),眼科抗组胺剂(即,萘甲唑啉(naphazoline),去氧肾上腺素(phenylephrine)和四氢唑啉(tetrahydrozoline)),眼用润滑剂,眼科甾类化合物(即,氟米龙(fluorometholone),泼尼松龙(prednisolone),氯替泼诺(loteprednol),地塞米松(dexamethasone),二氟泼尼酯(difluprednate),利美索龙(rimexolone),醋酸氟轻松(fluocinolone),甲羟松(medrysone)和去炎松(triamcinolone)),眼科麻醉剂(即,利多卡因(lidocaine),丙美卡因(proparacaine)和丁卡因(tetracaine)),眼科抗感染剂(即,左氧氟沙星(levofloxacin),加替沙星(gatifloxacin),环丙沙星(ciprofloxacin),莫西沙星(moxifloxacin),氯霉素(chloramphenicol),杆菌肽/多粘菌素b(bacitracin/polymyxin b),磺胺醋酰(sulfacetamide),妥布霉素(tobramycin),阿奇霉素(azithromycin),贝西沙星(besifloxacin),诺氟沙星(norfloxacin),磺胺异唑(sulfisoxazole),庆大霉素(gentamicin),碘苷(idoxuridine),红霉素(erythromycin),那他霉素(natamycin),短杆菌肽(gramicidin),新霉素(neomycin),氧氟沙星(ofloxacin),曲氟尿苷(trifluridine),更昔洛韦(ganciclovir),阿糖腺苷(vidarabine)),眼科抗炎剂(即,奈帕芬胺(nepafenac),酮咯酸(ketorolac),氟比洛芬(flurbiprofen),舒洛芬(suprofen),环孢菌素(cyclosporine),去炎松(triamcinolone),双氯芬酸(diclofenac)和溴芬酸(bromfenac)),和眼科抗组胺剂或解充血药(即,酮替芬(ketotifen),奥洛他定(olopatadine),依匹斯汀(epinastine),萘甲唑啉(naphazoline),色甘酸钠(cromolyn),四氢唑啉(tetrahydrozoline),吡嘧司特(pemirolast),贝他斯汀(bepotastine),萘甲唑啉(naphazoline),去氧肾上腺素(phenylephrine),奈多罗米(nedocromil),洛度沙胺(lodoxamide),去氧肾上腺素(phenylephrine),依美斯汀(emedastine)和氮卓斯汀(azelastine))。对于发作疾病,可以选择是抗惊厥药或抗癫痫药的神经药物,其包括、但不限于,巴比妥酸盐(barbiturate)抗惊厥药(即,扑米酮(primidone),美沙比妥(metharbital),甲苯比妥(mephobarbital),阿洛巴比妥(allobarbital),异戊巴比妥(amobarbital),阿普比妥(aprobarbital),苯烯比妥(alphenal),巴比妥(barbital),溴烯比妥(brallobarbital)和苯巴比妥(phenobarbital)),苯并二氮卓类(benzodiazepine)抗惊厥药(即,地西泮(diazepam),氯硝西泮(clonazepam)和劳拉西泮(lorazepam)),氨基甲酸酯(carbamate)抗惊厥药(即非尔氨酯(felbamate)),碳酸酐酶(carbonic anhydrase)抑制剂抗惊厥药(即,乙酰唑胺(acetazolamide),托吡酯(topiramate)和唑尼沙胺(zonisamide)),二苯并氮卓(dibenzazepine)抗惊厥药(即,卢非酰胺(rufinamide),卡马西平(carbamazepine)和奥卡西平(oxcarbazepine)),脂肪酸衍生物抗惊厥药(即,双丙戊酸钠(divalproex)和丙戊酸(valproic acid)),γ-氨基丁酸类似物(即,普瑞巴林(pregabalin),加巴喷丁(gabapentin)和氨己烯酸(vigabatrin)),γ-氨基丁酸再摄取抑制剂(即,噻加宾(tiagabine)),γ-氨基丁酸转氨酶抑制剂(即,氨己烯酸(vigabatrin),乙内酰脲抗惊厥药(即苯妥英(phenytoin),乙苯妥英(ethotoin),磷苯妥英(fosphenytoin)和美芬妥英(mephenytoin)),杂类抗惊厥药(即,拉科酰胺(lacosamide)和硫酸镁),孕酮类(即,黄体酮(progesterone)),唑烷二酮(oxazolidinedione)抗惊厥药(即,甲乙双酮(paramethadione)和三甲双酮(trimethadione)),吡咯烷抗惊厥药(即,左乙拉西坦(levetiracetam)),琥珀酰亚胺抗惊厥药(即,乙琥胺(ethosuximide)和甲琥按(methsuximide)),三嗪抗惊厥药(即,拉莫三嗪(lamotrigine)),和尿素抗惊厥药(即,苯乙酰脲(phenacemide)和苯丁酰脲(pheneturide))。
对于溶酶体贮积病,可以选择这样的神经药物,其自身或以其它方式模拟在疾病中受损的酶的活性。用于治疗溶酶体贮积病的示例性重组酶包括、但不限于在例如美国专利申请公开号2005/0142141中描述的那些(即,α-L-艾杜糖醛酸酶(iduronidase),艾杜糖醛酸-2-硫酸酯酶,N-硫酸酯酶,α-N-乙酰葡糖胺糖苷酶,N-乙酰-半乳糖胺-6-硫酸酯酶,β-半乳糖苷酶,芳基硫酸酯酶B,β-葡糖醛酸糖苷酶,酸性α-葡糖苷酶,葡糖脑苷脂酶,α-半乳糖苷酶A,己糖胺酶A,酸性神经磷脂酶,β-半乳糖脑苷脂酶,β-半乳糖苷酶,芳基硫酸酯酶A,酸性酰胺酶,天冬氨酸酰酶(aspartoacylase),棕榈酰-蛋白硫酯酶1和三肽酰氨肽酶1)。
对于淀粉样变性,可以选择这样的神经药物,其包括、但不限于,特异性地结合选自β分泌酶,tau,早老蛋白,淀粉样蛋白前体蛋白或其部分,淀粉样蛋白β肽或其低聚物或纤丝(fibril),死亡受体6(DR6),高度糖基化终产物受体(RAGE),帕金蛋白和亨廷顿蛋白的靶标的抗体或其它结合分子(包括、但不限于小分子,肽,适体,或其它蛋白质结合物);胆碱酯酶抑制剂(即,加兰他敏(galantamine),多奈哌齐(donepezil),利斯的明(rivastigmine)和他克林(tacrine));NMDA受体拮抗剂(即,美金刚(memantine)),单胺耗竭剂(monoaminedepletor)(即,丁苯那嗪(tetrabenazine));氢麦角碱(ergoloid mesylate);抗胆碱能抗帕金森病药(即,丙环定(procyclidine),苯海拉明(diphenhydramine),trihexylphenidyl,苯扎托品(benztropine),比哌立登(biperiden)和苯海索(trihexyphenidyl));多巴胺能抗帕金森病药(即,恩他卡朋(entacapone),司来吉兰(selegiline),普拉克索(pramipexole),溴隐亭(bromocriptine),罗替高汀(rotigotine),司来吉兰(selegiline),罗匹尼罗(ropinirole),雷沙吉兰(rasagiline),阿扑吗啡(apomorphine),卡比多巴(carbidopa),左旋多巴(levodopa),培高利特(pergolide),托卡朋(tolcapone)和金刚烷胺(amantadine));丁苯那嗪(tetrabenazine);抗炎药(包括、但不限于,非甾类抗炎药(即,吲哚美辛(indomethicin)和以上列出的其它化合物);激素(即,雌激素,孕酮和亮丙立德(leuprolide));维生素(即,叶酸和烟酰胺);dimebolin;高牛磺酸(homotaurine)(即,3-氨基丙磺酸;3APS);5-羟色胺受体活性调节剂(即,扎利罗登(xaliproden));干扰素和糖皮质激素。
对于病毒或微生物疾病,可以选择这样的神经药物,其包括、但不限于,抗病毒化合物(包括、但不限于,金刚烷抗病毒药(即,金刚乙胺(rimantadine)和金刚烷胺),抗病毒干扰素(即,聚乙二醇干扰素α-2b(peginterferon alfa-2b)),趋化因子(chemokine)受体拮抗剂(即,马拉韦罗(maraviroc)),整合酶链转移抑制剂(即,raltegravir),神经氨酸酶(neuraminidase)抑制剂(即,奥塞米韦(oseltamivir)和扎那米韦(zanamivir)),非核苷逆转录酶抑制剂(即,依法韦仑(efavirenz),依曲韦林(etravirine),地拉韦啶(delavirdine)和奈韦拉平(nevirapine)),核苷逆转录酶抑制剂(去羟肌苷加(tenofovir),阿巴卡韦(abacavir),拉米夫定(lamivudine),齐多夫定(zidovudine),司他夫定(stavudine),恩替卡韦(entecavir),恩曲他滨(emtricitabine),阿德福韦(adefovir),扎昔他宾(zalcitabine),替比夫定(telbivudine)和去羟肌苷(didanosine)),蛋白酶抑制剂(即,达芦那韦(darunavir),阿扎那韦(atazanavir),呋山那韦(fosamprenavir),替拉那韦(tipranavir),利托纳韦(ritonavir),奈芬纳韦(nelfinavir),氨普那韦(amprenavir),茚地那韦(indinavir)和沙奎那韦(saquinavir)),嘌呤核苷(即,伐昔洛韦(valacyclovir),泛昔洛韦(famciclovir),阿昔洛韦(acyclovir),利巴韦林(ribavirin),更昔洛韦(ganciclovir),缬更昔洛韦(valganciclovir)和西多福韦(cidofovir)),和杂类抗病毒药(即,恩夫韦肽(enfuvirtide),膦甲酸(foscarnet),帕利珠单抗(palivizumab)和福米韦生(fomivirsen)),抗生素(包括、但不限于,氨基青霉素(即,羟氨苄青霉素(amoxicillin),氨苄青霉素(ampicillin),苯唑西林(oxacillin),萘夫西林(nafcillin),氯唑西林(cloxacillin),双氯西林(dicloxacillin),flucoxacillin,替莫西林(temocillin),阿洛西林(azlocillin),羟苄青霉素(carbenicillin),替卡西林(ticarcillin),美洛西林(mezlocillin),哌拉西林(piperacillin)和巴氨西林(bacampicillin)),头孢菌素(cephalosporin)(即,头孢唑林(cefazolin),头孢氨苄(cephalexin),头孢噻吩(cephalothin),头孢孟多(cefamandole),头孢曲松(ceftriaxone),头孢噻肟(cefotaxime),头孢达肟(cefpodoxime),头孢他啶(ceftazidime),头孢羟氨苄(cefadroxil),头孢拉定(cephradine),氯碳头孢(loracarbef),头孢替坦(cefotetan),头孢唑肟(cefuroxime),头孢丙烯(cefprozil),头孢克洛(cefaclor)和头孢西丁(cefoxitin)),碳青霉烯/培南(carbapenem/penem)(即,亚胺培南(imipenem),美罗培南(meropenem),厄他培南(ertapenem),法罗培南(faropenem)和多利培南(doripenem)),单酰胺菌素(monobactam)(即,胺曲南(aztreonam),替吉莫南(tigemonam),norcardicin A和烟毒素-β-内酰胺(tabtoxinine-β-lactam)),与另一种β-内酰胺抗生素联合的β-内酰胺酶抑制剂(即,克拉维酸(clavulanic acid),三唑巴坦(tazobactam)和舒巴克坦(sulbactam)),氨基葡糖苷(即,阿米卡星(amikacin),庆大霉素(gentamicin),卡那霉素(kanamycin),新霉素(neomycin),奈替米星(netilmicin),链霉素,托普霉素(tobramycin)和巴龙霉素(paromomycin)),安沙霉素(ansamycin)(即,格尔德霉素(geldanamycin)和除莠霉素(herbimycin)),碳头孢烯(carbacephem)(即,氯碳头孢(loracarbef)),糖肽(即,替考拉宁(teicoplanin)和万古霉素(vancomycin)),大环内酯(即,阿奇霉素(azithromycin),克拉霉素(clarithromycin),地红霉素(dirithromycin),红霉素(erythromycin),罗红霉素(roxithromycin),醋竹桃霉素(troleandomycin),泰利霉素(telithromycin)和壮观霉素(spectinomycin)),单酰胺菌素(即,胺曲南(aztreonam)),喹诺酮(quinolone)(即,环丙沙星(ciprofloxacin),依诺沙星(enoxacin),加替沙星(gatifloxacin),左氧氟沙星(levofloxacin),利莫沙星(lomefloxacin),莫西沙星(moxifloxacin),诺氟沙星(norfloxacin),氧氟沙星(ofloxacin),曲伐沙星(trovafloxacin),格帕沙星(grepafloxacin),司帕沙星(sparfloxacin)和替马沙星(temafloxacin)),磺酰胺(即,磺胺米隆(mafenide),sulfonamidochrysoidine,乙酰磺胺(sulfacetamide),磺胺嘧啶(sulfadiazine),磺胺甲二唑(sulfamethizole),磺胺(sulfanilamide),柳氮磺吡啶(sulfasalazine),磺胺异唑(sulfisoxazole),甲氧苄啶(trimethoprim),甲氧苄啶(trimethoprim)和磺胺甲唑(sulfamethoxazole)),四环素(tetracycline)(即,四环素(tetracycline),地美环素(demeclocycline),多西环素(doxycycline),米诺环素(minocycline)和土霉素(oxytetracycline)),抗肿瘤药或细胞毒性抗生素(即,多柔比星(doxorubicin),米托蒽醌(mitoxantrone),博来霉素(bleomycin),柔红霉素(daunorubicin),更生霉素(dactinomycin),表柔比星(epirubicin),伊达比星(idarubicin),普利霉素(plicamycin),丝裂霉素(mitomycin),喷司他丁(pentostatin)和戊柔比星(valrubicin))和杂类抗菌化合物(即,杆菌肽(bacitracin),粘菌素(colistin)和多粘菌素B(polymyxin B)),抗真菌剂(即,甲硝唑(metronidazole),硝唑尼特(nitazoxanide),替硝唑(tinidazole),氯喹(chloroquine),双碘喹啉(iodoquinol)和巴龙霉素(paromomycin)),和抗寄生虫药(包括、但不限于,奎宁(quinine),氯喹(chloroquine),阿莫地喹(amodiaquine),乙胺嘧啶(pyrimethamine),磺胺多辛(sulphadoxine),百乐君(proguanil),甲氟喹(mefloquine),阿托伐醌(atovaquone),伯氨喹(primaquine),青蒿素(artemesinin),卤泛群(halofantrine),多西环素(doxycycline),克林霉素(clindamycin),甲苯达唑(mebendazole),双羟萘酸噻嘧啶(pyrantel pamoate),噻苯哒唑(thiabendazole),乙胺嗪(diethylcarbamazine),伊维菌素(ivermectin),利福平(rifampin),两性霉素B(amphotericin B),美拉胂醇(melarsoprol),efornithine和阿苯达唑(albendazole))。对于缺血,可以选择这样的神经药物,其包括、但不限于,溶血栓药(即,尿激酶,阿替普酶(alteplase),瑞替普酶(reteplase)和替奈普酶(tenecteplase)),血小板凝集抑制剂(即,阿司匹林(aspirin),西洛他唑(cilostazol),氯吡格雷(clopidogrel),普拉格雷(prasugrel)和双嘧达莫(dipyridamole)),他汀(statin)(即,洛伐他汀(lovastatin),普伐他汀(pravastatin),氟伐他汀(fluvastatin),罗舒伐他汀(rosuvastatin),阿托伐他汀(atorvastatin),辛伐他汀(simvastatin),西立伐他汀(cerivastatin)和匹伐他汀(pitavastatin)),和提高血液流动或血管弹性的化合物,包括例如血压药物。
对于行为疾病,神经药物可以选自行为修正化合物,其包括、但不限于,非典型抗精神病药(即,利哌立酮(risperidone),奥氮平(olanzapine),apripiprazole,喹硫平(quetiapine),帕潘立酮(paliperidone),阿塞那平(asenapine),氯氮平(clozapine),伊潘立酮(iloperidone)和齐拉西酮(ziprasidone)),吩噻嗪抗精神病药(即,丙氯拉嗪(prochlorperazine),氯丙嗪(chlorpromazine),氟奋乃静(fluphenazine),奋乃静(perphenazine),三氟拉嗪(trifluoperazine),硫利达嗪(thioridazine)和美索达嗪(mesoridazine)),噻吨(即,氨砜噻吨(thiothixene)),杂类抗精神病药(即,匹莫齐特(pimozide),锂(lithium),吗茚酮(molindone),氟哌啶醇(haloperidol)和洛沙平(loxapine)),选择性5-羟色胺再摄取抑制剂(即,西酞普兰(citalopram),依他普仑(escitalopram),帕罗西汀(paroxetine),氟西汀(fluoxetine)和舍曲林(sertraline)),5-羟色胺-去甲肾上腺素(norepinephrine)再摄取抑制剂(即,度洛西汀(duloxetine),文拉法辛(venlafaxine),地文拉法辛(desvenlafaxine)),三环抗抑郁药(即,多塞平(doxepin)),氯米帕明(clomipramine),阿莫沙平(amoxapine),去甲替林(nortriptyline),阿米替林(amitriptyline),曲米帕明(trimipramine),丙咪嗪(imipramine),普罗替林(protriptyline)和地昔帕明(desipramine)),四环抗抑郁药(即,米氮平(mirtazapine)和麦普替林(maprotiline)),苯基哌嗪抗抑郁药(即,曲唑酮(trazodone)和奈法唑酮(nefazodone)),单胺氧化酶抑制剂(即,异卡波肼(isocarboxazid),苯乙肼(phenelzine),司来吉兰(selegiline)和反苯环丙铵(tranylcypromine)),苯并二氮卓(即,阿普唑仑(alprazolam),艾司唑仑(estazolam),氟西泮(flurazeptam),氯硝西泮(clonazepam),劳拉西泮(lorazepam)和地西泮(diazepam)),去甲肾上腺素-多巴胺再摄取抑制剂(即,安非他酮(bupropion)),CNS兴奋剂(即,芬特明(phentermine),安非拉酮(diethylpropion),甲基苯丙胺(methamphetamine),右旋安非他命(dextroamphetamine),安非他命(amphetamine),哌醋甲酯(methylphenidate),右哌甲酯(dexmethylphenidate),利右苯丙胺(lisdexamfetamine),莫达非尼(modafinil),匹莫林(pemoline),苯甲曲秦(phendimetrazine),苄非他明(benzphetamine),苯甲曲秦(phendimetrazine),阿莫非尼(armodafinil),安非拉酮(diethylpropion),咖啡因(caffeine),阿托西汀(atomoxetine),多沙普仑(doxapram)和马吲哚(mazindol)),抗焦虑药/镇静药/催眠药(包括、但不限于,巴比妥酸盐(barbiturate)(即,司可巴比妥(secobarbital),苯巴比妥(phenobarbital)和甲苯比妥(mephobarbital)),苯并二氮(如上所述),和杂类抗焦虑药/镇静药/催眠药(即苯海拉明(diphenhydramine),羟丁酸钠(sodium oxybate),扎来普隆(zaleplon),羟嗪(hydroxyzine),水合氯醛(chloral hydrate),aolpidem,丁螺环酮(buspirone),多塞平(doxepin),左旋佐匹克隆(eszopiclone),雷美尔通(ramelteon),甲丙氨酯(meprobamate)和乙氯维诺(ethclorvynol))),分泌素(参见,例如,Ratliff-Schaub等,Autism 9:256-265(2005)),阿片样肽(参见,例如,Cowen等,J.Neurochem.89:273-285(2004)),和神经肽(参见,例如,Hethwa等,Am.J.Physiol.289:E301-305(2005))。
对于CNS炎症,可以选择治疗炎症自身的神经药物(即,非甾类抗炎剂如布洛芬或萘普生),或治疗炎症的潜在原因的神经药物(即,抗病毒或抗癌症药剂)。
在另一个实施方案中,所述脑效应物实体是完整或全长抗体。取决于其重链恒定结构域的氨基酸序列,可以将完整抗体分配到不同的”类别”。有五个主要类别的完整抗体:IgA,IgD,IgE,IgG和IgM,并且这些中的数个可以进一步被划分为亚类(同种型),例如,IgGl,IgG2,IgG3,IgG4,IgA和IgA2。对应于不同类别的抗体的重链恒定结构域分别被称为α,δ,ε,γ和μ。不同类别的免疫球蛋白的亚基结构和三维构型是公知的。在一个实施方案中,完整抗体缺少效应子功能。
用于生产抗体的技术是已知的,并且实例被提供在以上在本文件的定义部分中。在一个实施方案中,抗体是嵌合抗体、人源化抗体或人抗体或其抗原结合片段。
多种技术可用于确定单价结合实体与R/BBB的结合。一种这样的测定是酶联免疫吸附测定(ELISA),其用于确认与人R/BBB(及脑抗原)结合的能力。根据该测定,将包被有抗原(例如重组sR/BBB)的平板与包含针对R/BBB的单价结合实体的样品一起温育,并且测定单价结合实体与目的抗原的结合。
在一个方面,例如,通过已知方法如ELISA、蛋白印迹法等,测试本发明的单价结合实体的抗原结合活性。
在一个方面,使用X-射线结构测定的表位作图,测试本发明的单价结合实体对R/BBB的单抗原结合活性。
用于评价全身性地施用的血脑屏障穿梭体和/或缀合物的摄取以及血脑屏障穿梭体和/或缀合物的其它生物活性的测定,可以如在实施例中公开的或如关于目标血脑屏障穿梭体和/或缀合物已知的那样进行。使用例如微透析或毛细血管耗竭方法与标记的血脑屏障穿梭体和/或缀合物的ELISA或放射性测量的组合,也可以测量CNS的实质空间内的浓度。
药物制剂
通过以冻干制剂或水溶液形式与任选的药用载体、赋形剂或稳定剂混合(Remington's Pharmaceutical Sciences,第16版,Osol,A.编(1980)),制备根据本发明使用的血脑屏障穿梭体和/或缀合物的治疗制剂用于贮存。可接受的载体、赋形剂或稳定剂在所用剂量及浓度下对接受者无毒,且包括:缓冲液,例如磷酸盐、柠檬酸盐及其它有机酸;抗氧化剂,包括抗坏血酸及甲硫氨酸;防腐剂(例如氯化十八烷基二甲基苄铵、氯化六羟季铵、苯扎氯铵、苄索氯铵;苯酚、丁醇或苄醇;对羟基苯甲酸烷基酯,例如对羟基苯甲酸甲酯或对羟基苯甲酸丙酯;儿茶酚;间苯二酚;环己醇;3-戊醇;及间甲酚);低分子量(少于约10个残基)多肽;蛋白质,例如血清白蛋白、明胶或免疫球蛋白;亲水性聚合物,例如聚乙烯吡咯啶酮;氨基酸,例如甘氨酸、谷氨酰胺、天冬氨酸、组氨酸、精氨酸或赖氨酸;单糖、二糖和其它糖类,包括葡萄糖、甘露糖或糊精;螯合剂,例如EDTA;糖类,例如蔗糖、甘露醇、海藻糖或山梨醇;成盐平衡离子,例如钠离子;金属复合体(例如Zn-蛋白质复合体);和/或非离子表面活性剂,例如TWEENTM、PLURONICSTM或聚乙二醇(PEG)。
本文中的制剂在必要时也可以包含超过一种活性化合物,任选地包含具有不会不利地影响彼此的互补活性的那些。此种药物的类型和有效量取决于例如存在于制剂中的血脑屏障穿梭体和/或缀合物的量以及受试者的临床参数。以下讨论示例性的此种药物。
也可将活性成分截留于例如通过凝聚技术或通过界面聚合所制备的微囊中,例如,分别是在羟甲基纤维素或明胶微囊及聚-(甲基丙烯酸甲酯)微囊中,胶体释药系统(例如脂质体、白蛋白微球体、微乳液、纳米粒子及纳米囊)中或粗滴乳状液中。这些技术披露于Remington's Pharmaceutical Sciences,第16版,Osol,A.编(1980)中。
可制备持续释放制剂。持续释放制剂的合适实例包括含有抗体的固体疏水性聚合物的半渗透基质,该基质呈成形物品形式,例如薄膜或微囊形式。持续释放基质的例子包括聚酯、水凝胶(例如聚(2-羟乙基-甲基丙烯酸酯)或聚(乙烯醇))、聚交酯(美国专利第3,773,919号)、L-谷氨酸与γ乙基-L-谷氨酸酯的共聚物、不可降解的乙烯-乙酸乙烯酯、可降解的乳酸-乙醇酸共聚物,例如LUPRON DEPOTTM(由乳酸-乙醇酸共聚物与乙酸亮丙瑞林(leuprolide acetate)组成的可注射微球体)、和聚-D-(-)-3-羟基丁酸。
欲用于体内施用的制剂必须是无菌的。这可以通过借助无菌过滤膜过滤而轻易地实现。在一个实施方案中,制剂是等渗的。
本发明的血脑屏障穿梭体和/或缀合物可以被用于多种体内方法。例如,本发明提供将治疗性化合物运输穿过BBB的方法,所述方法包括将血脑屏障穿梭体和/或缀合物暴露于BBB,以使该单价结合实体将与其偶联的治疗性化合物运输穿过BBB。在另一个实施例中,本发明提供将神经疾病药物运输穿过BBB的方法,所述方法包括将血脑屏障穿梭体和/或缀合物暴露于BBB,以使该单价结合实体将与其偶联的神经疾病药物运输穿过BBB。在一个实施方案中,本文中的BBB是在哺乳动物(例如人)(例如患有神经疾病的人)中,所述神经疾病包括、但不限于:阿尔茨海默病(AD),卒中,痴呆,肌营养不良(MD),多发性硬化(MS),肌萎缩性侧索硬化(ALS),囊性纤维化,安吉尔曼综合征,利德尔综合征,帕金森病,皮克病,佩吉特病,癌症,外伤性脑损伤等。
在一个实施方案中,神经疾病选自:神经病,淀粉样变性,癌症(例如涉及CNS或脑的癌症),眼睛疾病或病症,病毒或微生物感染,炎症(例如CNS或脑的炎症),缺血,神经变性疾病,发作,行为疾病,溶酶体贮积症等。
神经疾病是神经系统的疾病或异常,其特征在于不适当的或不受控的神经信号传导或缺少神经信号传导,并且包括、但不限于,慢性疼痛(包括感受伤害的疼痛),由对身体组织的损伤引起的疼痛,包括癌相关的疼痛,神经性疼痛(由神经、脊髓或脑中的异常引起的疼痛),和精神性疼痛(完全或大部分与心理疾病相关),头痛,偏头痛,神经病,以及常常伴随这样的神经疾病的征状和综合征如眩晕或恶心。
淀粉样变性是一组与在CNS中的胞外蛋白质沉积物相关的疾病和病症,其包括、但不限于,继发性淀粉样变性,年龄相关性淀粉样变性,阿尔茨海默病(AD),轻度认知受损(mild cognitive impairment,MCI),雷维小体痴呆,唐氏综合征,遗传性脑出血伴淀粉样变性(Dutch型);Guam Parkinson-痴呆综合征状,脑淀粉样血管病,亨廷顿病,进行性核上性麻痹,多发性硬化;克-雅病,帕金森病,传递性海绵状脑病,HIV相关痴呆,肌萎缩性脊髓侧索硬化症(ALS),包涵体肌炎(inclusion-body myositis,IBM),和涉及β-淀粉样蛋白沉积的眼病(即,黄斑变性,玻璃疣相关视神经病变和白内障)。
CNS的癌症表征为一个或多个CNS细胞(即,神经细胞)的异常增殖,并且包括、但不限于,胶质瘤(glioma),多形性胶质母细胞瘤(glioblastoma multiforme),脑膜瘤(meningioma),星细胞瘤(astrocytoma),听神经瘤(acoustic neuroma),软骨瘤(chondroma),少突神经胶质瘤(oligodendroglioma),成神经管细胞瘤(medulloblastomas),神经节神经胶质瘤(ganglioglioma),神经鞘瘤(Schwannoma),神经纤维瘤(neurofibroma),成神经细胞瘤(neuroblastoma),和硬膜外、髓内或硬膜内肿瘤。
CNS的病毒或微生物感染包括、但不限于由以下引起的感染:病毒(即,流感,HIV,脊髓灰质炎病毒,风疹,),细菌(即,奈瑟氏球菌属(Neisseria sp.),链球菌属(Streptococcus sp.),假单胞菌属(Pseudomonas sp.),变形菌属(Proteus sp.),大肠杆菌(E.coli),金黄色葡萄球菌(S.aureus),肺炎球菌属(Pneumococcus sp.),脑膜炎球菌属(Meningococcus sp.),嗜血杆菌属(Haemophilus sp.),和结核分枝杆菌(Mycobacteriumtuberculosis))和其它微生物如真菌(即,酵母,新型隐球菌(Cryptococcusneoformans)),寄生虫(即,弓形虫(toxoplasma gondii))或变形虫(amoebas),导致CNS病理生理学,包括、但不限于,脑膜炎,脑炎,脊髓炎,血管炎和脓肿(abscess),其可以是急性的或慢性的。CNS的炎症是这样的炎症,其由对CNS的损伤导致,所述损伤可以是物理损伤(即,由于事故,手术,脑创伤,脊髓损伤,脑震荡(concussion)所致的)或由于一种或多种CNS的其它疾病或病症(即,脓肿,癌症,病毒或微生物感染)导致或与之相关的损伤。
本文中使用的CNS的缺血是指一组病症,其与脑部的异常血流或血管行为或其病因相关,并且包括、但不限于,局灶性脑缺血(focal brain ischemia),全局脑缺血(globalbrain ischemia),卒中(即,蛛网膜下出血和脑内出血(intracerebral hemorrhage)),和动脉瘤。
神经变性疾病是一组疾病和病症,其与CNS中神经细胞丧失功能或死亡相关,并且包括、但不限于,肾上腺脑白质营养不良(adrenoleukodystrophy),亚历山大病,阿尔珀斯病(Alper’s disease),肌萎缩性侧索硬化,运动失调性毛细血管扩张症(ataxiatelangiectasia),Batten病(Batten disease),科凯恩综合征,基层皮质变性(corticobasal degeneration),由淀粉样变性引起或与其相关的变性,弗里德赖希共济失调症(Friedreich’s ataxia),额颞叶变性(emporal lobar degeneration),Kennedy病(Kennedy’s disease),多系统萎缩,多发性硬化,原发性侧索硬化,进行性核上性麻痹,脊髓性肌萎缩,横贯性脊髓炎,雷夫叙姆病(Refsum’s disease),和脊髓小脑性共济失调。
CNS的发作疾病和病症涉及CNS中的不适当和/或异常电导,并且包括、但不限于,癫痫(即,失神发作(absence seizures),失张力发作(atonic seizures),良性运动性癫痫(benign Rolandic epilepsy),儿童期失神(childhood absence),阵挛发作(clonicseizures),复杂部分发作(complex partial seizures),额叶性癫痫(frontal lobeepilepsy),发热性癫痫发作(febrile seizures),婴儿痉挛(infantile spasms),少年肌阵挛性癫痫(juvenile myoclonic epilepsy),青少年期失神癫癎(juvenile absenceepilepsy),伦-格综合征(Lennox-Gastaut syndrome),兰-克综合征(Landau-KleffnerSyndrome),Dravet综合征(Dravet’s syndrome),Otahara综合征(Otahara syndrome),West综合征(West syndrome),肌肉阵挛性发作(myoclonic seizures),线粒体病(mitochondrial disorders),进行性肌阵挛性癫痫(progressive myoclonicepilepsies),精神性发作(psychogenic seizures),反射性癫痫(reflex epilepsy),Rasmussen综合征(Rasmussen's Syndrome),简单部分发作(simple partial seizures),继发性全身性癫痫发作(secondarily generalized seizures),颞叶癫痫(temporal lobeepilepsy),阵挛性发作(toniclonic seizures),强直发作(tonic seizures),精神运动发作(psychomotor seizures),边缘叶癫痫(limbic epilepsy),部分性癫痫发作(partial-onset seizures),全身发作性癫痫发作(generalized-onset seizures),癫痫持续状态(status epilepticus),腹型癫痫(abdominal epilepsy),失神型发作(akineticseizures),植物神经性发作(autonomic seizures),大量双侧肌阵挛(massive bilateralmyoclonus),月经性癫痫(catamenial epilepsy),跌倒发作(drop seizures),情绪性发作(emotional seizures),病灶性发作(focal seizures),发笑发作(gelastic seizures),贾克森扩布(Jacksonian March),拉福拉病(Lafora Disease),运动性发作(motorseizures),多病灶性发作(multifocal seizures),夜发作(nocturnal seizures),光敏性发作(photosensitive seizure),假性发作(pseudo seizures),感觉性发作(sensoryseizures),微小发作(subtle seizures),sylvan发作(sylvan seizures),戒断发作(withdrawal seizures),和视反射发作(visual reflex seizures))。
行为疾病是CNS的病症,其表征为就受折磨的受试者而言的异常行为,并且包括、但不限于:睡眠障碍(sleep disorders)(即,失眠(insomnia),深眠状态(parasomnias),夜惊(night terrors),昼夜节律睡眠障碍(circadian rhythm sleep disorders),和发作性睡病(narcolepsy)),心境障碍(mood disorders)(即,抑郁(depression),自杀性抑郁(suicidal depression),焦虑(anxiety),慢性情感障碍(chronic affectivedisorders),恐怖病(phobias),惊恐发作(panic attacks),强迫性疾病(obsessive-compulsive disorder),注意力缺陷伴多动疾病(attention deficit hyperactivitydisorder)(ADHD),注意缺陷障碍(attention deficit disorder)(ADD),慢性疲劳综合征(chronic fatigue syndrome),广场恐怖症(agoraphobia),创伤后应激障碍(post-traumatic stress disorder),双相性精神障碍(bipolar disorder)),进食障碍(即,厌食症(anorexia)或贪食症(bulimia)),精神病(psychoses),发育行为障碍(developmentalbehavioral disorder)(即,自闭症(autism),雷特综合征(Rett’s syndrome),Aspberger综合征(Aspberger’s syndrome)),人格障碍和精神障碍(即,精神分裂症(schizophrenia),妄想障碍(delusional disorder),等)。
溶酶体贮积症(Lysosomal storage disorder)是代谢病症,在一些情况中其与CNS相关或具有CNS特异性征状;这样的病症包括、但不限于泰-萨克斯病(Tay-Sachsdisease),戈谢病(Gaucher’s disease),法布里病(Fabry disease),粘多糖贮积症(I,II,III,IV,V,VI和VII型),糖原贮积病(glycogen storage disease),GM1神经节苷脂贮积症(GM1-gangliosidosis),异染性脑白质病变(metachromatic leukodystrophy),Farber病(Farber’s disease),卡纳范脑白质营养不良(Canavan’s leukodystrophy),和神经元蜡样脂褐素沉积症(neuronal ceroid lipofuscinoses)1型和2型,尼曼-皮克病(Niemann-Pick disease),Pompe病(Pompe disease),和克拉伯病(Krabbe’s disease)。
在一个方面,提供了用作药物的本发明的血脑屏障穿梭体和/或缀合物。在其它方面,提供了用于治疗神经疾病或病症(例如,阿尔茨海默病)的本发明的血脑屏障穿梭体和/或缀合物。在某些实施方案中,提供了用在治疗方法中的本发明的血脑屏障穿梭体和/或缀合物。在某些实施方案中,本发明提供了用在治疗具有神经疾病或病症的个体的方法中的本发明的血脑屏障穿梭体和/或缀合物,所述方法包括:给所述个体施用有效量的本发明的血脑屏障穿梭体和/或缀合物。根据任意上述实施方案的“个体”任选地是人。
在治疗中,本发明的血脑屏障穿梭体和/或缀合物可以单独使用或与其它药剂组合使用。例如,本发明的血脑屏障穿梭体和/或缀合物可以与至少一种另外的治疗剂共同施用。在某些实施方案中,另外的治疗剂是这样的治疗剂:其可以有效地治疗与采用本发明的血脑屏障穿梭体和/或缀合物所治疗的神经疾病相同或不同的神经疾病。示例性的另外的治疗剂包括、但不限于:以上所述的多种神经药物,胆碱酯酶抑制剂(如多奈哌齐,加兰他敏,利斯的明和他克林),NMDA受体拮抗剂(如丁苯那嗪),淀粉样蛋白β肽聚集抑制剂,抗氧化剂,γ-分泌酶调节物,神经生长因子(NGF)模拟物或NGF基因疗法,PPARy激动剂,HMS-CoA还原酶抑制剂(他汀类),丙嗪类,钙通道阻断剂,GABA受体拮抗剂,糖原合成酶激酶抑制剂,静脉内免疫球蛋白,毒蕈碱(muscarinic)受体激动剂,烟碱(nicrotinic)受体调节物,主动或被动淀粉样蛋白β肽免疫,磷酸二酯酶抑制剂,5-羟色胺受体拮抗剂和抗淀粉样蛋白β肽抗体。在某些实施方案中,因其减轻神经药物的一种或多种副作用的能力而选择至少一种另外的治疗剂。
这样的以上所述的组合疗法包括组合给药(其中两种以上治疗剂被包含在相同或分开的制剂中)和分别给药(其中,本发明的血脑屏障穿梭体和/或缀合物的给药可以发生在另外的治疗剂和/或佐剂的给药之前、同时和/或之后)。本发明的血脑屏障穿梭体和/或缀合物也可以与其它介入疗法组合使用,介入疗法诸如,但不限于,放射疗法,行为疗法,或本领域中已知的且对于待治疗或预防的神经疾病来说是合适的其它疗法。本发明的血脑屏障穿梭体和/或缀合物(以及任何另外的治疗剂)可以通过任何合适的方法给药,包括胃肠外给药,肺内给药和鼻内给药,并且,如果局部治疗需要,病灶内给药。胃肠外输注包括肌肉内、静脉内、动脉内、腹膜内或皮下给药。
给药可以是通过任何适合途径,例如通过注射,例如静脉内或皮下注射,部分地取决于给药是短期的还是长期的。本文中涵盖各种定量给药方案,包括,但不限于,单次给药或在多个时间点多次给药、推注给药及脉冲输注。
本发明的血脑屏障穿梭体和/或缀合物将以与良好医疗实践相一致的方式配制、定量给药和施用。在这方面考虑的因素包括待治疗的具体病症、待治疗的具体哺乳动物、个体患者的临床状态、病症的原因、递送试剂的位点、给药方法、给药时间安排、和医疗从业者已知的其它因素。本发明的血脑屏障穿梭体和/或缀合物不需要,但任选地,与目前用于预防或治疗所讨论病症的一种或多种药剂一起配制。所述其它药剂的有效量取决于制剂中存在的血脑屏障穿梭体和/或缀合物的量、病症或治疗的类型、和以上讨论的其它因素。这些一般以相同剂量,并使用如本文中所述的给药途径,或以本文中所述的剂量的约1-99%,或以通过经验/临床确定为合适的任意剂量和任何途径来使用。
为了预防或治疗疾病,本发明的血脑屏障穿梭体和/或缀合物的合适剂量(当单独或与一种或多种其它另外的治疗剂组合使用时)将取决于待治疗疾病的类型、血脑屏障穿梭体和/或缀合物的类型、疾病的严重性和进程、所述抗体是以预防目的施用还是以治疗目的施用、以前的治疗、患者的临床病史和对血脑屏障穿梭体和/或缀合物的应答,和主治医师的判断力。所述血脑屏障穿梭体和/或缀合物以一次治疗或经过一系列治疗合适地施用于患者。根据疾病的类型和严重性,约1μg/kg-15mg/kg(例如0.1mg/kg-10mg/kg)的血脑屏障穿梭体和/或缀合物可以是用于向患者施用的最初候选剂量,无论,例如,通过一次或多次分别施药,还是通过连续输注。一个典型的日剂量可以在约1μg/kg-100mg/kg或更多的范围内,其取决于上文提及的因素。为了重复施用数日或更长,根据病症,通常将持续治疗直至出现疾病征状的理想抑制。所述抗体的一个示范性剂量应该在约0.05mg/kg-约10mg/kg范围内。因此,约0.5mg/kg、2.0mg/kg、4.0mg/kg或10mg/kg(或其任意组合)的一个或多个剂量可以施用于患者。这样的剂量可以间隔地,例如每周或每三周施用(例如以使得患者接受约2-约20或例如约6个剂量的所述抗体)。可以施用最初较高的负荷剂量,随后是一个或多个较低的剂量。但是,其它治疗方案可以是有用的。该疗法的进展可以容易地通过常规技术和测定来监测。
制品
在本发明的另一个方面,提供一种制品,其包含可用于治疗和/或预防上述病症的材料。该制品包括容器和在容器上或与容器一起的标签或包装说明书(package insert)。适合的容器包括,例如,瓶子、小瓶、注射器、IV溶液包等。所述容器可以由各种材料诸如玻璃或塑料制成。容器装有组合物,所述组合物是单独地或与可有效用于治疗、预防和/或诊断所述病症的另一种组合物组合,并且可以具有无菌的存取口(例如,所述容器可以是具有可被皮下注射针刺穿的塞子的静脉输注液袋或小瓶)。组合物中至少一种活性试剂是本发明的血脑穿梭和/或缀合物。标签或包装说明书标明该组合物是用于治疗特定的病症。此外,所述制品可以包含(a)其中包含组合物的第一容器,其中所述组合物包含本发明的血脑屏障穿梭体和/或缀合物;和(b)其中包含组合物的第二容器,其中所述组合物包含另一种细胞毒性剂或其它的治疗剂。本发明的该实施方案中的制品还可以包括包装说明书,所述包装说明书指明所述组合物可以用于治疗特定病症。可替换地,或另外地,所述制品还可以包括第二(或第三)容器,所述第二(或第三)容器包含药用缓冲剂,如抑菌注射用水(BWFI),磷酸盐缓冲盐水,林格氏液(Ringer’s solution)和葡萄糖溶液。从商业和用户立场,它还可以包括所需的其它材料,包括其它缓冲剂、稀释剂、滤膜、针头和注射器。
该制品任选地还包括包装说明书,其具有关于在受试者中治疗神经疾病的说明,其中该说明指示利用如本文中所公开的血脑屏障穿梭体和/或缀合物的治疗来治疗神经疾病,并且任选地指示所述血脑屏障穿梭体和/或缀合物由于其对R/BBB的单价结合模式而具有改善的穿过BBB的摄取。
实施例
实施例1:表达质粒的制备
基础/标准哺乳动物表达质粒的描述
通过瞬时转染人胚胎肾细胞(HEK 293),表达期望的蛋白。为了表达期望的基因/蛋白(例如抗体-Fab多聚体蛋白),使用包含下述功能元件的转录单元:
●得自人巨细胞病毒(P-CMV)的立即早期增强子和启动子,包括内含子A,
●人重链免疫球蛋白5’-非翻译区(5’UTR),
●鼠免疫球蛋白重链信号序列(SS),
●要表达的基因/蛋白(例如全长抗体重链),和
●牛生长激素多腺苷酸化序列(BGH pA)。
除了包括要表达的期望基因的表达单位/盒以外,基础/标准哺乳动物表达质粒含有:
●得自载体pUC18的复制起点,其允许在大肠杆菌中复制该质粒,和
●β-内酰胺酶基因,其在大肠杆菌中赋予氨苄西林抗性。
构建编码下述抗体-sFab融合多肽/蛋白的表达质粒:
四价Mab31-scFab(8D3)(图1C)(Mab31=识别Mab31的Aβ.INN的人单克隆抗体=更
汀芦单抗(Gantenerumab))
重链(10132_pPM284_Mab31(IgG1)-(G4S)4-VL-Ck-(G4S)6-GG-VH-CH1)
(Seq.Id.No.1):
Mab31-scFab(8D3)重链融合蛋白的组成:
●不含C-端Lys的Mab31人IgG1重链
●甘氨酸丝氨酸-接头
●小鼠8D3抗-转铁蛋白抗体的可变轻链结构域(VL)变体(L596V和L598I)(Boado,R.J.Zhang,Y.Wang,Y和Pardridge,W.M.,Biotechnology and Bioengineering(2009)102,1251-1258)
●人C-κ轻链
●甘氨酸丝氨酸-接头
●小鼠8D3抗-转铁蛋白抗体的可变重链结构域(VH)(Boado,R.J.Zhang,Y.Wang,Y和Pardridge,W.M.,Biotechnology and Bioengineering(2009)102,1251-1258)
●人IgG1 CH3重链结构域
轻链(5170-VL-Mab31-BsmI-L2-Neo-BGHpA)(Seq.Id.No.2)
Mab31轻链的组成
-Mab31人Cκ轻链
三价Mab31-scFab(8D3)(图1B)
突出物重链(10134_pPM287_Mab31(IgG1)_突出物_SS_-(G4S)4-VL-Ck-(G4S)6-GG-VH-CH1)(Seq.Id.No.3)
突出物Mab31-scFab(8D3)重链融合蛋白的组成
●不含C-端Lys的Mab31人IgG1重链,其含有用于形成额外二硫键的CH3突出物突变T366W和S354C突变
●甘氨酸丝氨酸-接头
●小鼠8D3抗-转铁蛋白抗体的可变轻链结构域(VL)变体(L596V和L598I)(Boado,R.J.Zhang,Y.Wang,Y和Pardridge,W.M.,Biotechnology and Bioengineering(2009)102,1251-1258)
●人C-κ轻链
●甘氨酸丝氨酸-接头
●小鼠8D3抗-转铁蛋白抗体的可变重链结构域(VH)(Boado,R.J.Zhang,Y.Wang,Y和Pardridge,W.M.,Biotechnology and Bioengineering(2009)102,1251-1258)
●人IgG1CH3重链结构域
孔洞重链(10133_pPM286_Mab31(IgG1)_孔洞_SS)(Seq.Id.No.4)
孔洞Mab31重链融合蛋白的组成
●Mab31人IgG1重链,其含有用于形成额外二硫键的CH3孔洞突变T366S、Y407V和L368A以及Y349C突变
轻链(5170-VL-Mab31-BsmI-L2-Neo-BGHpA)(Seq.Id.No.2)
Mab31轻链的组成
-Mab31人Cκ轻链
实施例2:单和双Mab31-Fab构建体的纯化
通过瞬时转染在F17培养基(Invitrogen Corp.)中培养的HEK293细胞(从人胚胎肾细胞系293衍生出),制备抗体链。为了转染,使用“293-Fectin”转染试剂(Invitrogen)。从2种(四价Mab31-scFab(8D3))或3种(三价Mab31-scFab(8D3))不同质粒表达抗体链,所述质粒分别编码四价Mab31-scFab(8D3)重链和Mab31对应轻链、或突出物和孔洞三价Mab31-scFab(8D3)重链和Mab31对应轻链。在转染后,以等摩尔质粒比率使用所述2种或3种质粒。如在生产商的说明书中所述,进行转染。在转染后7天,收获含有抗体融合蛋白的细胞培养物上清液。在纯化之前,将上清液冷冻储存。
从经过滤的细胞培养物上清液纯化蛋白。将上清液施加于蛋白A Sepharose柱(GEHealthcare),并用PBS(pH 7.4)洗涤。用100mM柠檬酸盐缓冲液(pH 3.0)洗脱抗体,随后立即将样品中和至pH6.5。浓缩以后,通过尺寸排阻色谱法(Superdex 200;GE Healthcare)将聚集的蛋白和其它副产物与单体抗体分离在20mM组氨酸、140mM NaCl(pH 6.0)中。在分析型SEC(TSK G3000SWXL)上和在基于芯片的毛血管电泳系统(CE-SDS,LabChipGX,测径器)上分析每个单独级分,以定量不完全装配的分子和其它副产物。将不含副产物的单体抗体级分合并。使用MILLIPOREAmicon Ultra(30分子量截止)离心浓缩器浓缩以后,在-80℃储存蛋白。通过UV蛋白测定、CE-SDS、尺寸排阻色谱法、质谱法以及通过内毒素测定,进行终产物的分析表征。
实施例3:单Fab和双Fab构建体的ELISA结合数据
通过间接ELISA,评估mAb31-8D3构建体与小鼠转铁蛋白受体(mTfR)的结合。为此目的,将重组mTfR(细胞外结构域;Sino Biological)以在PBS中的1μg/mL包被至Maxisorb微孔滴定板(Nunc)上在4℃过夜。在1%Crotein-C/PBS(封闭缓冲液;Roche)中在室温封闭1h并用0.1%吐温-20/PBS(洗涤缓冲液)洗涤4次以后,将mAb31-8D3构建体以在封闭缓冲液中的0.01-150nM之间的浓度加入孔中,并在室温温育1h。4个洗涤步骤以后,通过以在封闭缓冲液(1RT)中的1:10,000稀释度加入抗-人-IgG-HRP(Jackson Immunoresearch)来检测构建体,随后洗涤6次并在TMB(Sigma)中温育。用1N HCl停止显色以后,在450nm读出吸光度。
图3表明,二价mAb31-8D3-dFab与mTfR的结合与8D3 IgG的结合相当,而单价构建体mAb31-8D3-sFab显示出降低的亲和力。
通过ELISA证实mAb31的功能性。简而言之,将Aβ(1-40)以在PBS中的7μg/mL包被在Maxisorp平板上在37℃保持3天,以产生纤丝状Aβ,然后在室温干燥3h。将平板用在PBS(封闭缓冲液)中的1%Crotein C和0.1%RSA在室温封闭1h,然后用洗涤缓冲液洗涤1次。将mAb31构建体以在封闭缓冲液中至多100nM的浓度加入,并在4℃温育过夜。4个洗涤步骤以后,如上所示检测构建体。
图4表明,mAb31-8D3构建体(sFab和dFab)以与未修饰的mAb31相当的亲和力结合固定化的Aβ纤丝。
实施例4:仅单Fab构建体穿过BBB和并将斑块染色
脑切片和免疫组织化学染色:
在PBS灌注以后准备脑,并根据Paxinos和Franklin的脑图集,切割在侧向~1.92至1.68毫米之间的矢向冷冻切片。使用Leica CM3050S低温恒温器,在-15℃在20微米的标称厚度制作脑切片,并放在预冷的载玻片(Superfrost plus,Menzel,德国)上。对于每个脑,将3个间隔80微米的切片放在相同载玻片上。
将切片在PBS中再水合5分钟,随后用预冷却至-20℃的100%丙酮浸渍2min。在室温进行所有其它步骤。将带有脑切片的载玻片用PBS(pH 7.4)洗涤,并如下封闭非特异性的结合位点:在Ultra V block(LabVision)中连续温育5分钟,随后进行PBS洗涤,并在高效封闭溶液(BioGenex)中与在PBS中的2%正常山羊血清一起温育20min。将载玻片与浓度为20微克/ml(在含有2%正常山羊血清的PBS(pH 7.4)中)的第二抗体一起直接温育1小时,所述第二抗体是亲和纯化的与Alexa Fluor 555染料(#A-21433,批号54699A,MolecularProbes)缀合的山羊抗-人IgG(具有重链和轻链特异性)。用PBS充分洗涤以后,通过与0.5微克/ml的BAP-2(一种Roche自制鼠单克隆抗体,其针对与Alexa Fluor 488染料缀合的Aβ)一起在含有高效封闭溶液(BioGenex)和10%正常绵羊血清的PBS中温育1小时,对Aβ斑块进行双标记,由此评估斑块定位。PBS洗涤以后,通过在含有4mM CuSO4的50mM乙酸铵(pH 5)中温育30分钟进行淬灭,减少脂褐素的自发荧光。用双蒸馏水冲洗载玻片以后,用ConfocalMatrix(Micro Tech Lab,奥地利)包埋载玻片。
共焦显微术
拍摄每只PS2APP-小鼠的脑的每个切片的3个图像,所述小鼠具有在额皮质(一级运动皮质的区域)中的含有斑块的区域。用具有1Airy的针孔设置的Leica TCS SP5共焦系统记录图像。
在30%激光功率,用经调节的光电倍增管增益和偏移(通常,分别为770V和-0%),在相同波谱条件(488nm激发和500-554nm带通发射)下捕获用Alexa Fluor 488染料免疫标记的斑块。
在570-725nm范围内的窗口(其覆盖施加的检测抗体的发射波长范围),在561nm激发激光线,记录在组织切片的可利用表面上的结合的第二Alexa Fluor 555抗体。为了图像获取,将仪器设置保持恒定,以允许试验的人抗-Aβ抗体的比较强度测量;具体地为激光功率、扫描速度、增益和偏移。将激光功率设定为30%,并且PMT增益的设置通常为850V,且标称偏移为0%。这能够用相同设置实现微弱地和强烈地染色的斑块的显影。获取频率是在400Hz。
以512x512像素分辨率,用在水中的HCX PL APO 20x 0.7 IMM UV物镜将共焦扫描记录为单个光学层,并且交互地控制在垂直轴上的光学测量深度,以确保在组织切片内的成像。拍摄位于额皮质的第2-5层中的淀粉样蛋白-β斑块的图像,并定量荧光强度。
统计分析
将免疫阳性区域显影为TIFF图像,并进行加工用于用ImageJ 1.45版(NIH)定量荧光强度和面积(以像素为单位来测量)。为了定量,在每个图像中减去5的背景强度,并滤出小于5平方像素的阳性区域。将选择的等值面的总荧光强度确定为单个单独阳性区域的强度的总和,并通过将总强度除以分析的像素的数目来计算平均像素强度。
用Microsoft Excel(Redmond/WA,USA),从得自9个图像的所有测量的等值面计算平均值和标准差值,所述图像取自每只动物的3个不同切片。使用Student氏t检验(对于组对比)或Mann-Whitney检验,进行统计分析。
将10mg/ml mAb31(图1A的构建体)、13.3mg/kg sFab-mAb31(图1B的构建体)和16.7mg/kg dFAb-mAb31(图1C的构建体)注射进小鼠尾巴静脉中,且在8小时以后,用PBS灌注脑。如上所述制备切片,并用山羊抗-人IgG染色。对于mAb31构建体,几乎没有检测到特异性信号(图4A)。对于sFab-mAb31,检测到斑块和毛细血管的广泛染色(图4B),而对于dFab-mAb31,仅检测到毛细血管的染色(图4C)。这清楚地表明,单价结合模式(针对转铁蛋白受体的sFab-mAb31)远远更有效地携带构建体穿过脑内皮细胞到达BBB处。在图5中显示了二价结合分子(dFab-mAb31)的定量。数据表明,对于dFab-mAb31构建体而言,不存在斑块染色的增加,由于构建体的毛细血管积累,仅存在总强度的增加。
实施例5:单Fab构建体的脑暴露的定量
在实施例4中描述了实验规程。使用10mg/ml mAb31(图1A的构建体)和13.3mg/kgsFab-mAb31(图1B的构建体),在图6中显示了sFab-mAb31脑暴露的定量。在注射sFab-mAb31构建体以后8小时,与mAb31相比存在大量摄取(约55倍增加)。在使用25mg/ml mAb31(图1A的构建体)和33.3mg/kg sFab-mAb31(图1B的构建体)给药后24小时,得到类似的数据。图6也显示了sFab-mAb31的暂时毛细血管染色,解释了靶向效应和随时间对BBB的穿过。所有这些数据是非常显著的,如在图6中所示。
图7显示了低剂量的mAb31(图1A的构建体)和sFab-mAb31(图1B的构建体)构建体的数据。再一次,仅sFab-mAb31构建体能够穿过脑内皮细胞并将脑中的斑块染色。最大效应已经在给药后8小时达到。对于mAb31构建体,仅在较高剂量(10mg/kg)和相对长的时间(7天),才存在与脑中的Aβ斑块结合的信号增加的趋势(图7)。所有这些数据是非常显著的,如在图7中所示。
实施例6:双Fab构建体对细胞表面TfR的特异性减量调节
实验细节:以6-孔板形式培养bEnd3细胞。在汇合后2-3天,用dFab-mAb31、sFab-mAb31处理24小时,对照不处理。然后,将培养基除去/抽吸,并将细胞用5ml/孔的冰冷的PBS(-MgCl)(-CaCl)(Gibco 14190-094)洗涤2次。加入1ml胰蛋白酶/EDTA(Lonza CC-5012)/孔,并在37℃温育15分钟,直到所有细胞脱离。用1ml胰蛋白酶中和溶液(冰冷的)(LonzaCC-5002)停止反应。将2ml胰蛋白酶/EDTA+中和溶液收集在50ml Falcon试管中,并保持在冰上。将细胞在1400rpm在4℃离心10分钟。将沉淀物再悬浮于50ml冰冷的bEnd3培养基(DMEM-12(Gibco 31331)+10%FBS)中。将细胞在4℃在1400rpm离心10分钟。将沉淀物再悬浮于3ml冰冷的FACS-缓冲液(BD 554656)中。细胞计数:a)sFab试管(2,5x105个细胞/ml)生存力:47%,b)dFab试管(3.18x105个细胞/ml)生存力:55%,c)对照试管(4.6x105个细胞/ml)生存力:57%。FACS将1x105个细胞/埃彭道夫管染色,分布并离心(4℃,10min,1500rpm)。抽吸上清液;a)CD71-PE(克隆R17217-IgG2a单克隆抗体)(圣克鲁斯sc-52504)20微升抗体/沉淀物(染色体积100微升)用冰冷的FACS-缓冲液(BD 554656)补充至100微升,b)CD31-APC(BD 551262)(大鼠抗小鼠IgG2a(200微克/ml))5微克抗体/沉淀物(染色体积100微升)用冰冷的FACS-缓冲液(BD 554656)补充至100微升,c)将8D3-Alexa488(1:50)(染色体积100微升)在冰冷的FACS-缓冲液(BD 554656)中稀释,d)Alexa488、APC和PE的同种型对照(都得自BD)。在暗处在冰上温育1小时。用冰冷的FACS-缓冲液补充至1.5ml并离心(4℃,10min,1500rpm)。将沉淀物用1.5ml冰冷的FACS-缓冲液洗涤2次,最后将沉淀物重新悬浮于500微升PBS中。使用仪器Guava Flow Cytometry,进行FACS测量。数据表明,双(dFab)构建体(图8B)似乎会减量调节细胞表面上的转铁蛋白受体。这在该测定方案中是不可检测的,单个(sFab)构建体(图8A)指示单价结合模式对决定脑内皮细胞上的细胞表面处的转铁蛋白受体的量的细胞运输和重复利用没有直接影响。
实施例7:单和双Fab构建体的体内细胞内筛选
用下述构建体MAb31(10mg/kg)、sFab-MAb31(13.3mg/kg)或dFab-MAb31(17.44mg/kg)静脉内注射(尾巴注射)APPswe/PS2转基因小鼠。以MAb31作为参照,注射剂量反映了分子大小。注射后15分钟或8小时,将小鼠用CO2安乐死,并如下处理。将心脏的右心房切开,使得血液和灌注溶液可以流出。将左心室切开,将管饲探针#10插入主动脉中。注射大约20mlPBS(~10ml/min,室温),随后注射30ml 2%的PFA在PBS中的溶液。将脑取出,并在相同灌注盐水(perfusat)中温育另外7h00。使用振动切片机制备100微米脑游离漂浮切片,将其用于免疫荧光染色。首先将切片渗透化处理,并使用PBS-0.3%Triton X-100-10%驴血清封闭。然后,将切片与在PBS-5%驴血清中稀释的指定第一抗体一起温育过夜。按照生产商的推荐,使用分子探针第二抗体。使用Leica SP5共焦显微镜获取图像,将Imaris软件用于图像处理和3D重构。
这些数据解释了脑内皮细胞对周围施用的sFab-MAb31和dFab-MAb31的摄取。使用与Alexa 555偶联的山羊抗-人抗体,检测MAb31、sFab-MAb31和dFab-MAb31。如在图9中所示,sFab-MAb31(图9A)和dFab-MAb31(图9B)在注射后15min都将脑脉管系统染色,它们的分布没有差异。注射后8h00,sFab-MAb31到达实质并将淀粉样蛋白斑块染色(图9C箭头),而dFab-MAb31(图9D)停留在脑脉管系统内,类似于15min时间点。用dFab-MAb31没有检测到实质中的淀粉样蛋白斑块。
图10:为了控制在研究中使用的所有构建体的完整性,使用MAb31(图10A)、sFab-MAb31(图10B)或dFab-MAB31(图10C)进行18个月脑冷冻切片的染色。结果表明,所有3种构建体检测到转基因小鼠的脑中的淀粉样蛋白斑块。
图11-12:高分辨率共焦显微术表明,sFab(图11)和dFab-MAb31(图12)没有将脑毛细血管的腔侧染色,但是被包含在囊泡样结构(其穿过内皮细胞的腔膜)内和内皮细胞胞质溶胶内。在图11和图12中的箭头指示在内皮细胞细胞核的近腔侧上含有sFab或dFab-MAb31构建体的囊泡。总之,这些数据提示,sFab-MAb31和dFab-MAb31可以进入内皮细胞中,但是仅sFab-MAb31可以穿过脉管系统和达到淀粉样蛋白斑块。
本发明的方法和组合物提供了显著改善抗体的一部分的途径,所述抗体分布进CNS中并因而更容易地在CNS中达到治疗浓度。本发明的方法和组合物是新颖的,且显著改善穿过BEC内的不同细胞器的效率,使用最佳的和稳定的细胞内途径/分选到达近腔侧。
实施例8:对于穿过BBB而言关键性的单价受体结合模式
抗-Aβ单克隆抗体mAb31是非常特异性的和有效的Aβ斑块结合剂,从而给我们提供了定量脑实质内的靶标啮合的有力读出。我们使用PS2APP双转基因淀粉样变性模型来研究两种脑穿梭构建体与mAb31亲本抗体相比的脑暴露的量。将三种变体以10mg/kg静脉内地注射,并通过定量注射后8小时存在于斑块处的抗体的量来确定脑暴露的程度。对于dFab构建体,与mAb31相比没有检测到斑块染色的显著增加(图13A)。但是,对于sFab构建体,与亲本mAb31抗体相比,存在斑块染色的大量增加。对于sFab构建体,基于使用经标记的第二抗体的荧光强度定量,在淀粉样蛋白斑块处的靶标啮合提高了超过50倍。而sFab构建体表现出广泛的斑块染色(图13D),dFab仅在微血管中是可检测的(图13C),从而指示dFab构建体靶向并进入脑微血管,但是没有在近腔侧逃逸。我们研究了2.66mg/kg低剂量的sFab构建体的靶标啮合能力,并将体内暴露时间延长至7天。在8小时内达到最大斑块染色,随后在单次注射以后的至少一周中持续斑块结合(图13E)。
在以前的研究中,已经证实亲本mAb31在注射后7天达到最大斑块结合。微血管结构中的染色的定量指示,sFab构建体在BBB处的定位是非常暂时的,从而解释了所述构建体穿过该屏障的相对快速的速率。2mg/kg的亲本抗体mAb31在注射后7天(图13F)和等摩尔浓度的sFab构建体(图13G)的代表性斑块染色图像解释了斑块结合的增加,该成就用sFab脑穿梭构建体达到。sFab构建体仅显示与溶酶体隔室一起的微小共定位,这可能反映了TfR向溶酶体的正常组成性运输。我们的体外研究也表明sFab构建体的重复利用和胞吞转运。总之,这些发现提示,sFab构建体不会干扰TfR的正常运输。相反,dFab构建体显示出与溶酶体隔室一起的强共定位,但是没有胞吞转运活性,无论是在体外还是在体内。
实施例9:增加的穿过BBB的抗体递送转化成增强的体内效能
在下一组实验中,我们研究了使用单价结合模式引起的脑暴露的显著增加是否会改善抗-Aβ抗体在长期治疗研究中的体内效能。我们每周注射sFab构建体和对照亲本抗体mAb31持续3个月。在前5个月研究中,已经证实20mg/kg的治疗性抗体mAb31会减少斑块负荷。基于在图14中显示的数据,我们选择2个低剂量来研究改善的脑暴露是否会导致增强的体内效能。在最终的靶斑块结合指示,在两种剂量,与亲本mAb31抗体相比,存在与sFab构建体更强的靶标啮合(图14A-D)。在基线以及在媒介物、低剂量亲本mAb31和低剂量sFab构建体处理以后,定量APPPS2双转基因小鼠中的淀粉样变性程度。在这些低剂量,用亲本单克隆mAb31没有检测到体内效应(图14E),这基于历时5个月的先前长期研究而预见到。相反,用2.67mg/kg低剂量的sFab构建体,观察到皮质和海马中的斑块数目的显著减少。即使在0.53mg/kg的远远更低的剂量(图14E),观察到支持sFab构建体的趋势,特别是在皮质中,尽管它没有达到统计显著性。斑块尺寸的二级分析揭示了小斑块的斑块数目的更显著的减少,这与mAb31的作用模式相一致。这些数据指示,由TfR结合的单价模式实现的增加的脑穿透会导致治疗性抗体在阿尔茨海默病病理学的慢性动物模型中的效能的显著改善。
实施例10:不同抗体融合蛋白在体外对TfR+BaF3细胞的效应子功能(ADCC)
使用表达转铁蛋白受体的BaF3细胞(DSMZ,#CLPZ04004)(TfR+)作为由不同的抗体融合分子诱导的抗体依赖性的细胞毒性(ADCC)实验的靶细胞。
简而言之,将1x104个BaF3细胞接种在圆底96孔中,并任选地在有或没有抗体融合蛋白存在下以3:1的效应物/靶标比率与人NK92效应细胞(高亲和力CD16克隆7A2F3;RocheGlycArt)一起共培养。温育(37℃,5%CO2)4小时以后,如通过死亡/染色细胞对乳酸脱氢酶(LDH)的释放所测量的,评估细胞毒性。对于该细胞,在250xg离心5min,并将50μl上清液转移至平底板。加入50μl LDH反应混合物(Roche LDH反应混合物,目录号11644793001;RocheDiagnostics GmbH),并将反应物在37℃、5%CO2温育20min。随后,在Tecan Sunrise读数器上在492/620nm波长测量吸光度。
一式三份地试验所有样品,并基于下述对照计算结果:
-仅靶细胞(+培养基)
-最大LDH释放:靶细胞+3%Triton-X
-自发释放:靶细胞+NK细胞(3:1的E:T)
通过下式计算特异性的ADCC/裂解百分比:
图15:含有与Fc C-端融合的TfR scFab片段的抗体融合没有诱导ADCC。通过定量LDH释放,测量NK92介导的BA/F3小鼠红白血病细胞的杀死。仅融合构建体(其具有结合TfR的Fab部分,呈“常规”“N-端至Fc”取向)诱导显著的ADCC,而呈相反取向的脑穿梭构建体是沉默的。构建体:8D3-IgG(全长8D3 IgG)、OA-8D3(8D3 IgG的单个重链)、mAb31(图1A的抗体)、mAb31-8D3 sFab(图1B的构建体)、mAb31-8D3-dFab(图1C的构建体)。
实施例11:mTfR抗体8D3的表位作图
借助于与鼠转铁蛋白受体1的细胞外结构域的序列(90-763)对应的重叠的、固定化的肽片段(长度:15个氨基酸,转移:3个氨基酸)的文库,进行单克隆抗体8D3的表位作图。为了制备肽阵列,采用Intavis CelluSpotsTM技术。在该方案中,用自动化的合成仪(Intavis MultiPep RS)在改性纤维素盘(其在合成后溶解)上合成肽。然后将保持与大分子纤维素共价连接的各个肽的溶液印迹到包被的显微镜载玻片上。利用9-芴基甲氧基羰基(Fmoc)化学法在384-孔合成板中在氨基-改性纤维素盘上逐步进行CelluSpotsTM合成。在每个偶联循环中,用DIC/HOBt在DMF中的溶液活化对应的氨基酸。在偶联步骤之间,用乙酸酐、二异丙基乙胺和1-羟基苯并三唑的混合物将未反应的氨基加帽。合成结束后,将纤维素盘转移至96-孔板,并用三氟乙酸(TFA)、二氯甲烷、三异丙基硅烷(TIS)和水的混合物处理进行侧链去保护。除去裂解溶液以后,将纤维素结合的肽用TFA、TFMSA、TIS和水的混合物溶解,用二异丙基醚沉淀,并再悬浮于DMSO中。随后使用Intavis载玻片印迹机器人将这些肽溶液印迹到Intavis CelluSpotsTM载玻片上。
对于表位分析,将制备的载玻片用乙醇洗涤,然后用Tris-缓冲盐水(TBS;50mMTris,137mM NaCl,2.7mM KCl,pH 8)洗涤,再用5mL 10x Western Blocking Reagent(Roche Applied Science)、2.5g在TBS中的蔗糖、0.1%吐温20在4℃进行封闭步骤16h。洗涤(TBS+0.1%吐温20)以后,将载玻片用抗体8D3在TBS+0.1%吐温20中的溶液(1μg/mL)在环境温度温育2h。洗涤以后,将载玻片温育,用抗-小鼠第二HRP-抗体(1:20000在TBS-T中)检测,随后与化学发光底物鲁米诺一起温育,并用LumiImager(Roche Applied Science)显影。定量ELISA-阳性的SPOT,并通过对应肽序列的分配,鉴别抗体结合表位。
图16:8D3结合小鼠转铁蛋白受体的细胞外结构域中的3种独特肽。通过在携带固定化的mTfR肽的CelluSpot载玻片上温育的抗体的化学发光检测,揭示了有3个氨基酸重叠的抗体8D3-15聚体肽的结合。框:被8D3结合的肽#373、374和376。
表1:在肽绘图实验中被8D3结合的mTfR细胞外结构域肽序列.
肽ID | 肽序列 | 序列号 |
373 | I-G-Q-N-M-V-T-I-V-Q-S-N-G-N-L | Seq.Id.No.14 |
374 | N-M-V-T-I-V-Q-S-N-G-N-L-D-P-V | Seq.Id.No.15 |
376 | Q-S-N-G-N-L-D-P-V-E-S-P-E-G-Y | Seq.Id.No.16 |
在本文中描述了一组针对血脑屏障受体、尤其是转铁蛋白受体(TfR)的生物治疗剂构建体,其可以以治疗上有关的剂量递送治疗剂(包括抗体、蛋白、肽和小分子)穿过BBB。某些经工程改造的生物治疗剂构建体的分布在注射后数小时内从脑血管空间改变至实质空间,从而指示这些特定构建体利用最佳运输途径穿过BEC,以实现显著量的生物治疗剂被胞吞转运穿过BEC以到达实质。生物治疗剂构建体在CNS中的摄取和分布的程度完全依赖于与血脑屏障受体、尤其是TfR的单价结合模式。当TfR通过生物治疗剂构建体与R/BBB的结合而变得二聚化时,没有检测到实质空间内的可检测的水平。使用本发明的方法工程改造的单Fab抗-Aβ单克隆构建体的单次全身剂量不仅导致在脑中的显著抗体摄取,而且急剧增加与病理性淀粉样蛋白斑块结合的抗-Aβ单克隆的染色。但是,使用针对R/BBB的双Fab结合构建体,没有检测到CNS内的可检测的水平。在本申请中描述的事实和实验解释了在使用针对R/BBB的单价结合模式增加生物治疗剂(诸如抗体)向CNS中的摄取背后的关键性促成机制。首先,双(或多聚体)抗-R/BBB结合模式通过快速地减量调节在腔侧上的细胞表面上的R/BBB而限制脑摄取,从而减少可以被吸收进脉管系统中的总量抗-R/BBB,这是有效的BBB穿过的第一步。其次,双(或多聚体)抗-R/BBB结合模式会在BEC中在细胞内地诱导独特的错误分选,其阻止构建体到达近腔侧。惊人的是,与R/BBB的单价结合会改善脑摄取和分布,在从脉管系统向CNS内的淀粉样蛋白斑块的定位中观察到完全转移。其次,生物治疗剂构建体对R/BBB的经工程改造的单价结合模式会确保R/BBB向腔侧的重复利用,以允许摄取额外融合多肽构建体并运输至近腔侧和进入实质中。第三,单价结合模式生物治疗剂构建体在IgG的Fc部分的C-末端处经过工程改造,这会阻止治疗性单克隆抗体的原始形式,其在大多数情况下对于体内效力而言是关键性的。这还可以如下实现:与在本申请内描述的IgG的其它部分连接。这是有利的,因为已经开发了具有确立的临床前和临床效力的IgG单克隆抗体,其可以掺入该运输系统中,而不损害确立的功能和效力。此外,受体介导的基于运输(RMT)的单价靶向R/BBB技术打开了CNS疾病的宽范围潜在治疗剂的大门。本发明提供了工程改造穿透BBB的治疗剂的方法,所述治疗剂保留现有的IgG形式,具有经证实的治疗活性,其极大地改善了所述治疗剂穿过BBB的运输和CNS分布。
公开的氨基酸序列
氨基酸序列名称 | 序列识别编号(Seq.Id.No.) |
Mab31重链-scFab(8D3) | 1 |
Mab31轻链 | 2 |
突出物Mab31重链-scFab(8D3) | 3 |
孔洞Mab31重链-scFab(8D3) | 4 |
Mab 31V<sub>H</sub> CDR1 | 5 |
Mab 31V<sub>H</sub> CDR2 | 6 |
Mab 31V<sub>H</sub> CDR3 | 7 |
Mab 31V<sub>L</sub> CDR1 | 8 |
Mab 31V<sub>L</sub> CDR2 | 9 |
Mab 31V<sub>L</sub> CDR3 | 10 |
Mab 31V<sub>H</sub> | 11 |
Mab 31V<sub>L</sub> | 12 |
肽接头(G<sub>4</sub>S)<sub>6</sub>G<sub>2</sub> | 13 |
8D3表位作图肽373 | 14 |
8D3表位作图肽374 | 15 |
8D3表位作图肽376 | 16 |
肽接头(G<sub>4</sub>S)<sub>4</sub> | 17 |
Claims (42)
1.一种血脑屏障穿梭体,其包含脑效应物实体、接头和一个结合血脑屏障受体的单价结合实体,其中所述接头将所述效应物实体与所述结合血脑屏障受体的单价结合实体偶联。
2.根据权利要求1所述的血脑屏障穿梭体,其中所述结合血脑屏障受体的单价结合实体选自由蛋白、多肽和肽组成的组。
3.根据权利要求1或2所述的血脑屏障穿梭体,其中所述结合血脑屏障受体的单价结合实体包含选自由以下组成的组的分子:血脑屏障受体配体、scFv、Fv、sFab、VHH,优选sFab。
4.根据权利要求1-3所述的血脑屏障穿梭体,其中所述血脑受体选自由以下组成的组:转铁蛋白受体、胰岛素受体、胰岛素样生长因子受体、低密度脂蛋白受体相关的蛋白8、低密度脂蛋白受体相关的蛋白1和结合肝素的表皮生长因子样生长因子,优选转铁蛋白受体。
5.根据权利要求1-4所述的血脑屏障穿梭体,其中所述结合血脑屏障受体的单价结合实体包含一个针对转铁蛋白受体的scFab,优选是识别包含在Seq.Id.No.14、15或16的氨基酸序列中的转铁蛋白受体中的表位的scFab。
6.根据权利要求1或5所述的血脑屏障穿梭体,其中所述脑效应物实体选自由神经疾病药物、神经营养因子、生长因子、酶、细胞毒性剂、针对脑靶标的抗体、针对脑靶标的单克隆抗体、针对脑靶标的肽组成的组。
7.根据权利要求6所述的血脑屏障穿梭体,其中所述脑靶标选自由以下组成的组:β-分泌酶1、Aβ、表皮生长因子、表皮生长因子受体2、Tau、磷酸化的Tau、载脂蛋白E4、α突触核蛋白、α突触核蛋白的寡聚片段、CD20、亨廷顿蛋白、朊病毒蛋白、富含亮氨酸的重复序列激酶2、帕金蛋白、早老蛋白2、γ分泌酶、死亡受体6、淀粉样蛋白前体蛋白、p75神经营养因子受体和胱天蛋白酶6。
8.根据权利要求1-7所述的血脑屏障穿梭体,其中所述脑效应物实体选自由蛋白、多肽和肽组成的组。
9.根据权利要求8所述的血脑屏障穿梭体,其中所述结合血脑受体的单价结合实体通过所述接头偶联至所述脑效应物实体的C-末端。
10.根据权利要求1-9所述的血脑屏障穿梭体,其中所述脑效应物实体包含针对脑靶标的全长抗体,优选全长IgG。
11.根据权利要求10所述的血脑屏障穿梭体,所述血脑屏障穿梭体包含作为脑效应物实体的全长IgG抗体、接头和一个作为结合血脑受体的单价结合实体的scFab,其中所述scFab通过所述接头偶联至所述IgG抗体的重链之一的Fc部分的C-末端。
12.根据权利要求10或11所述的血脑屏障穿梭体,其中所述效应物实体是针对Aβ的全长抗体。
13.根据权利要求12所述的血脑屏障穿梭体,其中所述针对Aβ的抗体包含:(a)H-CDR1,其包含Seq.Id.No.5的氨基酸序列,(b)H-CDR2,其包含Seq.Id.No.6的氨基酸序列,(c)H-CDR3,其包含Seq.Id.No.7的氨基酸序列,(d)L-CDR1,其包含Seq.Id.No.8的氨基酸序列,(e)L-CDR2,其包含Seq.Id.No.9的氨基酸序列,和(f)L-CDR3,其包含Seq.Id.No.10的氨基酸序列。
14.根据权利要求13所述的血脑屏障穿梭体,其中所述针对Aβ的抗体包含:包含Seq.Id.No.11的氨基酸序列的VH结构域,和包含Seq.Id.No.12的氨基酸序列的VL结构域。
15.根据权利要求10-11所述的血脑屏障穿梭体,其中所述效应物实体是针对磷酸化的Tau的全长抗体,且所述单价结合实体是一个针对转铁蛋白受体的scFab。
16.根据权利要求10或11所述的血脑屏障穿梭体,其中所述效应物实体是针对α突触核蛋白的全长抗体,且所述单价结合实体是一个针对转铁蛋白受体的scFab。
17.根据权利要求1-16所述的血脑屏障穿梭体,其中所述接头是肽接头,优选是具有至少20个氨基酸长度的氨基酸序列的肽,更优选具有25-50个氨基酸的长度。
18.根据权利要求1-7所述的血脑屏障穿梭体,其中所述结合血脑屏障受体的单价结合实体包含CH2-CH3Ig实体和一个结合血脑屏障受体的sFab,其中所述sFab通过第二接头偶联至CH2-CH3Ig实体的C-末端。
19.根据权利要求18所述的血脑屏障穿梭体,所述血脑屏障穿梭体包含所述脑效应物实体、所述接头、所述CH2-CH3Ig结构域、所述第二接头和一个结合血脑屏障受体的sFab,其中所述脑效应物实体通过第一接头偶联至所述CH2-CH3Ig结构域的N-末端,且所述sFab通过第二接头偶联至所述CH2-CH3Ig结构域的C-末端。
20.根据权利要求18或19所述的血脑屏障穿梭体,其中所述CH2-CH3Ig实体是CH2-CH3IgG实体。
21.一种分离的核酸,其编码根据权利要求1-20所述的血脑屏障穿梭体。
22.一种宿主细胞,其包含根据权利要求21所述的核酸。
23.一种药物制剂,其包含根据权利要求1-20所述的血脑屏障穿梭体和药用载体。
24.用作药物的根据权利要求1-20所述的血脑屏障穿梭体。
25.根据权利要求1-20所述的血脑屏障穿梭体在制备药物中的用途。
26.根据权利要求25所述的用途,其中所述药物用于治疗神经变性疾病,优选阿尔茨海默病。
27.用于运输脑效应物实体穿过血脑屏障的根据权利要求1-20所述的血脑屏障穿梭体。
28.一种用于运输脑效应物实体穿过血脑屏障的融合蛋白,其包含CH2-CH3Ig实体、接头和一个针对血脑屏障受体的sFab,其中所述sFab通过所述接头偶联至CH2-CH3Ig实体的C-末端。
29.根据权利要求28所述的用于运输脑效应物实体穿过血脑屏障的融合蛋白,其中所述脑效应物实体选自由以下组成的组:神经疾病药物、神经营养因子、生长因子、酶、细胞毒性剂、选自由scFv、Fv、scFab、Fab、VHH、F(ab’)2组成的组的针对脑靶标的抗体片段或肽。
30.根据权利要求28或29所述的用于运输脑效应物实体穿过血脑屏障的融合蛋白,其中所述针对血脑屏障受体的sFab是针对转铁蛋白受体的sFab,优选是识别包含在Seq.Id.No.14、15或16的氨基酸序列中的转铁蛋白受体中的表位的scFab。
31.根据权利要求28-30所述的用于运输脑效应物实体穿过血脑屏障的融合蛋白,其中所述接头是肽接头。
32.根据权利要求28-31所述的融合蛋白,其中所述CH2-CH3Ig实体是CH2-CH3IgG实体。
33.一种分离的核酸,其编码根据权利要求28-32所述的融合蛋白。
34.一种宿主细胞,其包含根据权利要求33所述的核酸。
35.一种缀合物,其包含根据权利要求28-32所述的用于运输脑效应物实体穿过血脑屏障的融合蛋白和通过接头与所述融合蛋白的CH2-CH3Ig实体的N-末端偶联的脑效应物实体。
36.根据权利要求35所述的缀合物,其中所述脑效应物实体选自由蛋白、多肽和肽组成的组。
37.根据权利要求36所述的缀合物,其中所述效应物实体的C-末端通过接头偶联至CH2-CH3Ig实体的N-末端。
38.一种药物制剂,其包含根据权利要求35-37所述的缀合物和药用载体。
39.用作药物的根据权利要求35-37所述的缀合物。
40.根据权利要求35-37所述的缀合物在制备药物中的用途。
41.根据权利要求40所述的用途,其中所述药物用于治疗神经变性疾病,优选阿尔茨海默病。
42.如前文所述的发明。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP12182181.3 | 2012-08-29 | ||
EP12182181 | 2012-08-29 | ||
CN201380042265.1A CN104520329A (zh) | 2012-08-29 | 2013-08-26 | 血脑屏障穿梭体 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201380042265.1A Division CN104520329A (zh) | 2012-08-29 | 2013-08-26 | 血脑屏障穿梭体 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN109053901A true CN109053901A (zh) | 2018-12-21 |
Family
ID=46963437
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201380042265.1A Pending CN104520329A (zh) | 2012-08-29 | 2013-08-26 | 血脑屏障穿梭体 |
CN201810972126.3A Pending CN109053901A (zh) | 2012-08-29 | 2013-08-26 | 血脑屏障穿梭体 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201380042265.1A Pending CN104520329A (zh) | 2012-08-29 | 2013-08-26 | 血脑屏障穿梭体 |
Country Status (27)
Country | Link |
---|---|
US (2) | US20150322149A1 (zh) |
EP (2) | EP2890712B1 (zh) |
JP (3) | JP6219956B2 (zh) |
KR (4) | KR20150039798A (zh) |
CN (2) | CN104520329A (zh) |
AU (3) | AU2013307406B2 (zh) |
BR (1) | BR112015004512B1 (zh) |
CA (1) | CA2879496C (zh) |
DK (1) | DK2890712T3 (zh) |
ES (1) | ES2733324T3 (zh) |
HK (1) | HK1205521A1 (zh) |
HR (1) | HRP20191153T1 (zh) |
HU (1) | HUE045144T2 (zh) |
IL (2) | IL237064A0 (zh) |
LT (1) | LT2890712T (zh) |
MX (2) | MX367126B (zh) |
MY (1) | MY178542A (zh) |
NZ (1) | NZ703585A (zh) |
PL (1) | PL2890712T3 (zh) |
PT (1) | PT2890712T (zh) |
RS (1) | RS58928B1 (zh) |
RU (3) | RU2663120C2 (zh) |
SG (2) | SG10201702702VA (zh) |
SI (1) | SI2890712T1 (zh) |
TR (1) | TR201909156T4 (zh) |
WO (1) | WO2014033074A1 (zh) |
ZA (1) | ZA201500346B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110101847A (zh) * | 2019-05-23 | 2019-08-09 | 北京豪思生物科技有限公司 | 转铁蛋白的应用及包含转铁蛋白的组合物 |
Families Citing this family (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG188190A1 (en) | 2010-08-03 | 2013-04-30 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
LT3378535T (lt) | 2011-10-28 | 2023-02-27 | Prothena Biosciences Limited | Humanizuoti antikūnai, atpažįstantys alfa-sinukleiną |
BR112014018561A8 (pt) | 2012-01-27 | 2017-07-11 | Neotope Biosciences Ltd | Anticorpo; ácido nucleico; célula hospedeira; composição farmacêutica; uso de um anticorpo; método para produção de um anticorpo; e método para produção de uma linhagem celular que produz um anticorpo |
JP6883944B2 (ja) | 2012-03-14 | 2021-06-09 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 多重特異性抗原結合分子およびその使用 |
RU2663120C2 (ru) * | 2012-08-29 | 2018-08-01 | Ф.Хоффманн-Ля Рош Аг | Шаттл для гематоэнцефалического барьера |
UA118441C2 (uk) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
US10513555B2 (en) | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
ES2821904T3 (es) | 2013-11-21 | 2021-04-28 | Hoffmann La Roche | Anticuerpos anti-alfa-sinucleína y procedimientos de uso |
RU2019134445A (ru) | 2013-12-20 | 2019-12-20 | Ф. Хоффманн-Ля Рош Аг | Улучшенные способы получения рекомбинантного полипептида |
PL3083680T3 (pl) | 2013-12-20 | 2020-06-29 | F. Hoffmann-La Roche Ag | Humanizowane przeciwciała przeciwko białku tau(pS422) i sposoby stosowania |
ES2895752T3 (es) | 2014-01-03 | 2022-02-22 | Hoffmann La Roche | Anticuerpos biespecíficos anti-hapteno/anti-receptor de la barrera hematoencefálica, complejos de los mismos y su uso como lanzaderas a través de la barrera hematoencefálica |
CA2932547C (en) | 2014-01-06 | 2023-05-23 | F. Hoffmann-La Roche Ag | Monovalent blood brain barrier shuttle modules |
JP6744856B2 (ja) * | 2014-04-08 | 2020-08-19 | プロセナ・バイオサイエンシズ・リミテッド | α−シヌクレインを認識する抗体を含む血液脳関門シャトル |
AR100978A1 (es) * | 2014-06-26 | 2016-11-16 | Hoffmann La Roche | LANZADERAS CEREBRALES DE ANTICUERPO HUMANIZADO ANTI-Tau(pS422) Y USOS DE LAS MISMAS |
US10093733B2 (en) | 2014-12-11 | 2018-10-09 | Abbvie Inc. | LRP-8 binding dual variable domain immunoglobulin proteins |
SG10201913762QA (en) | 2015-05-04 | 2020-03-30 | Cytomx Therapeutics Inc | Anti-cd71 antibodies, activatable anti-cd71 antibodies, and methods of use thereof |
TW201710286A (zh) | 2015-06-15 | 2017-03-16 | 艾伯維有限公司 | 抗vegf、pdgf及/或其受體之結合蛋白 |
CA2989637C (en) * | 2015-06-19 | 2023-01-10 | Eisai R&D Management Co., Ltd. | Cys80 conjugated immunoglobulins |
DK3313879T3 (da) | 2015-06-24 | 2022-03-14 | Hoffmann La Roche | Anti-transferrinreceptor-antistoffer med tilpasset affinitet |
JP6619460B2 (ja) | 2015-06-24 | 2019-12-11 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | ヒト化抗タウ(pS422)抗体及び使用法 |
JP7021955B2 (ja) * | 2015-06-24 | 2022-03-03 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | Her2及び血液脳関門受容体に特異的な三重特異性抗体及び使用方法 |
AR106189A1 (es) * | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
MX2018003822A (es) * | 2015-10-02 | 2018-06-22 | Hoffmann La Roche | Anticuerpos biespecificos contra el cd20 humano y el receptor de transferrina humano y metodos de uso. |
EP3782639B1 (en) * | 2015-12-08 | 2022-07-20 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for internalizing enzymes |
CA3028035A1 (en) | 2016-07-14 | 2018-01-18 | Bioarctic Ab | Brain delivery protein |
US10702589B2 (en) | 2016-10-04 | 2020-07-07 | Ann And Robert H. Lurie Children's Hospital Of Chicago | Compositions and methods of treating neurological disorder and stress-induced conditions |
WO2018102657A1 (en) * | 2016-12-02 | 2018-06-07 | Weiner David B | Dna antibody constructs for use against ebola virus |
RU2711912C2 (ru) * | 2016-12-15 | 2020-01-23 | Федеральное государственное бюджетное научное учреждение "Федеральный исследовательский центр "Красноярский научный центр Сибирского отделения Российской академии наук" (ФИЦ КНЦ СО РАН) | Аптамер, проходящий через гематоэнцефалический барьер головного мозга мыши |
US20190352335A1 (en) * | 2016-12-19 | 2019-11-21 | Hanmi Pharm. Co., Ltd. | Brain targeting long-acting protein conjugate |
CA3048601A1 (en) | 2016-12-26 | 2018-07-05 | Kyowa Hakko Kirin Co., Ltd. | Antibody which binds to myelin oligodendrocyte glycoprotein |
EA039807B1 (ru) | 2017-01-06 | 2022-03-16 | ЭйБиЭл БИО ИНК. | Антитело к -синуклеину и его применение |
US11702466B2 (en) | 2017-01-30 | 2023-07-18 | National Research Council Of Canada | Fusion protein comprising a blood-brain barrier (BBB)-crossing single domain antibody Fc5, an immunoglobulin Fc fragment and a beta-amyloid binding polypeptide (ABP) |
US10143187B2 (en) | 2017-02-17 | 2018-12-04 | Denali Therapeutics Inc. | Transferrin receptor transgenic models |
IL268660B2 (en) * | 2017-02-17 | 2024-03-01 | Denali Therapeutics Inc | Polypeptides that bind to a transgenic transferrin receptor, polynucleotides encoding them, methods for their preparation and use |
US10457717B2 (en) | 2017-02-17 | 2019-10-29 | Denali Therapeutics Inc. | Engineered polypeptides |
CN110637029A (zh) * | 2017-05-18 | 2019-12-31 | 豪夫迈·罗氏有限公司 | 减少治疗性抗体的应用相关的副反应 |
CA3072035A1 (en) * | 2017-08-10 | 2019-02-14 | Denali Therapeutics Inc. | Engineered transferrin receptor binding polypeptides |
WO2019036725A2 (en) | 2017-08-18 | 2019-02-21 | Adrx, Inc. | PEPTIDE INHIBITORS OF TAU AGGREGATION |
CN107412747B (zh) * | 2017-08-24 | 2018-05-22 | 北京亦贝安生物医药科技有限公司 | 一种含有乳铁蛋白和唾液酸的复方制剂 |
CN107410495B (zh) * | 2017-08-24 | 2018-06-01 | 北京亦贝安生物医药科技有限公司 | 一种酸性乳糖酶和锌的复方制剂及其制备方法 |
JP7403441B2 (ja) * | 2017-09-14 | 2023-12-22 | デナリ セラピューティクス インコーポレイテッド | 抗trem2抗体及びその使用方法 |
CR20200129A (es) | 2017-10-02 | 2020-08-22 | Denali Therapeutics Inc | Proteínas de fusión que comprenden enzimas de terapia de reemplazo de enzimas |
WO2019074892A1 (en) | 2017-10-09 | 2019-04-18 | Wisconsin Alumni Research Foundation | ANTIBODIES TARGETING GLIOBLASTOME STRAIN TYPE CELLS AND METHODS OF USE |
WO2019089395A1 (en) | 2017-11-02 | 2019-05-09 | Ossianix, Inc. | Improved tfr-selective binding peptides capable of crossing the blood brain barrier |
AU2018385230B2 (en) * | 2017-12-14 | 2022-10-13 | Abl Bio Inc. | Bispecific antibody to a-syn/IGF1R and use thereof |
US10688191B2 (en) | 2018-01-19 | 2020-06-23 | Hr Biomed, Llc | Delivery of a chemotherapy agent across the blood-brain barrier |
KR102012448B1 (ko) * | 2018-02-01 | 2019-08-20 | (주)프론트바이오 | 트리메토벤자미드 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 신경병증 통증의 예방 또는 치료용 약학적 조성물 |
EP3777894A4 (en) * | 2018-03-30 | 2022-04-06 | Hanmi Pharm. Co., Ltd. | LONG-ACTING BRAIN-TARGETING PROTEIN CONJUGATE, METHOD FOR PREPARING IT AND COMPOSITION CONTAINING IT |
ES2929416T3 (es) | 2018-06-21 | 2022-11-29 | Novo Nordisk As | Nuevos compuestos para el tratamiento de la obesidad |
EP3816291A4 (en) | 2018-06-26 | 2022-03-16 | Kyowa Kirin Co., Ltd. | CHONDROITIN SULFATE PROTEOGLYCAN-5 BINDING ANTIBODIES |
KR20210027295A (ko) | 2018-06-26 | 2021-03-10 | 쿄와 기린 가부시키가이샤 | 세포 부착 분자3에 결합하는 항체 |
KR20210074279A (ko) * | 2018-08-22 | 2021-06-21 | 데날리 테라퓨틱스 인크. | 항-her2 폴리펩타이드 및 이의 사용방법 |
JP2021534790A (ja) * | 2018-08-30 | 2021-12-16 | ネクスモス カンパニー リミテッドNexmos Co., Ltd. | 血液脳関門を通過するアプタマー及びその応用 |
JP7206524B2 (ja) | 2018-10-26 | 2023-01-18 | モガム・インスティテュート・フォー・バイオメディカル・リサーチ | Idsを含む融合タンパク質及びその使用 |
JP7446342B2 (ja) * | 2019-06-19 | 2024-03-08 | エフ. ホフマン-ラ ロシュ アーゲー | 所定の構成の複数の発現カセットの標的化組込みによって三価の抗体を発現する細胞を生成するための方法 |
MX2021015648A (es) | 2019-06-19 | 2022-02-03 | Hoffmann La Roche | Metodo para la generacion de una celula que expresa un anticuerpo multiespecifico multivalente mediante integracion dirigida de multiples casetes de expresion en una organizacion definida. |
US20220257542A1 (en) * | 2019-07-30 | 2022-08-18 | Frontbio Inc. | Pharmaceutical composition comprising trimethobenzamide or pharmaceutically acceptable salt thereof as active ingredient for preventing or treating neuropathic pain |
EP4028048A1 (en) | 2019-09-09 | 2022-07-20 | F. Hoffmann-La Roche AG | Glucocerebrosidase mutants |
KR102247568B1 (ko) | 2019-10-11 | 2021-05-04 | 재단법인 대구경북첨단의료산업진흥재단 | 집속초음파 조사 시스템 및 집속초음파를 이용한 혈액뇌장벽 개방 조절 방법 |
BR112022012230A2 (pt) | 2019-12-23 | 2022-08-30 | Denali Therapeutics Inc | Variantes de progranulina |
JPWO2021167107A1 (zh) | 2020-02-22 | 2021-08-26 | ||
WO2021170540A1 (en) | 2020-02-25 | 2021-09-02 | Vib Vzw | Leucine-rich repeat kinase 2 allosteric modulators |
CN116916947A (zh) | 2020-10-14 | 2023-10-20 | 戴纳立制药公司 | 包含磺基葡糖胺磺基水解酶的融合蛋白和其方法 |
BR112023025904A2 (pt) | 2021-06-11 | 2024-02-27 | Bioarctic Ab | Molécula de ligação biespecífica |
EP4373853A2 (en) * | 2021-07-21 | 2024-05-29 | Icahn School of Medicine at Mount Sinai | Anti-fsh antibodies for neurodegenerative diseases |
AU2022329794A1 (en) | 2021-08-19 | 2024-02-22 | Jcr Pharmaceuticals Co., Ltd. | Human transferrin receptor–binding peptide |
CN118201966A (zh) | 2021-08-24 | 2024-06-14 | 肽梦想株式会社 | 人转铁蛋白受体结合抗体-肽缀合物 |
EP4396231A1 (en) | 2021-09-01 | 2024-07-10 | Biogen MA Inc. | Anti-transferrin receptor antibodies and uses thereof |
KR20230048240A (ko) * | 2021-10-01 | 2023-04-11 | 서울대학교산학협력단 | 혈액 뇌장벽 투과용 펩타이드 및 이의 용도 |
KR102575322B1 (ko) * | 2021-12-31 | 2023-09-08 | 주식회사 아임뉴런 | 뇌혈관장벽 투과성 융합 단백질 및 이의 용도 |
WO2023128702A1 (ko) * | 2021-12-31 | 2023-07-06 | 주식회사 아임뉴런 | 뇌혈관장벽 투과성 융합 단백질 및 이의 용도 |
WO2023198661A1 (en) | 2022-04-12 | 2023-10-19 | F. Hoffmann-La Roche Ag | Fusion proteins targeted to the central nervous system |
WO2024008755A1 (en) | 2022-07-04 | 2024-01-11 | Vib Vzw | Blood-cerebrospinal fluid barrier crossing antibodies |
WO2024080843A1 (ko) * | 2022-10-14 | 2024-04-18 | 주식회사 아임뉴런 | 뇌혈관장벽 투과성 융합 단백질 및 이의 용도 |
WO2024091079A1 (ko) * | 2022-10-28 | 2024-05-02 | 주식회사 아임뉴런 | 뇌혈관장벽 투과성 융합 단백질 및 이의 용도 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050147613A1 (en) * | 1999-06-16 | 2005-07-07 | Boston Biomedical Research Institute | Immunological control of beta-amyloid levels in vivo |
WO2012075037A1 (en) * | 2010-11-30 | 2012-06-07 | Genentech, Inc. | Low affinity blood brain barrier receptor antibodies and uses therefor |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
MX9204374A (es) | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | Anticuerpo recombinante y metodo para su produccion. |
ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
ATE244763T1 (de) | 1992-02-11 | 2003-07-15 | Cell Genesys Inc | Erzielen von homozygotem durch zielgerichtete genetische ereignisse |
US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
GB9603256D0 (en) | 1996-02-16 | 1996-04-17 | Wellcome Found | Antibodies |
PT994903E (pt) | 1997-06-24 | 2005-10-31 | Genentech Inc | Metodos e composicoes para glicoproteinas galactosiladas |
CA2307166A1 (en) | 1997-10-31 | 1999-05-14 | Genentech, Inc. | Methods and compositions comprising glycoprotein glycoforms |
ES2532910T3 (es) | 1998-04-02 | 2015-04-01 | Genentech, Inc. | Variantes de anticuerpos y fragmentos de los mismos |
JP4334141B2 (ja) | 1998-04-20 | 2009-09-30 | グリカート バイオテクノロジー アクチェンゲゼルシャフト | 抗体依存性細胞傷害性を改善するための抗体のグリコシル化操作 |
BR0008758A (pt) | 1999-01-15 | 2001-12-04 | Genentech Inc | Variantes de polipeptìdeos parentais com funçãoefetora alterada, polipeptìdeos, composição ácidonucleico isolado, vetor, célula hospedeira,método para produzir uma variante depolipeptìdeo, método para o tratamento de umadesordem em mamìferos e método para produziruma região fc variante |
CN100390288C (zh) | 2000-04-11 | 2008-05-28 | 杰南技术公司 | 多价抗体及其应用 |
HUP0700103A3 (en) | 2001-08-03 | 2012-09-28 | Glycart Biotechnology Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
US20030157108A1 (en) | 2001-10-25 | 2003-08-21 | Genentech, Inc. | Glycoprotein compositions |
US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
US6849032B2 (en) * | 2002-11-20 | 2005-02-01 | Fitness Botics, Inc. | Exercise apparatus simulating skating motions |
US20050142141A1 (en) | 2002-11-27 | 2005-06-30 | Pardridge William M. | Delivery of enzymes to the brain |
MXPA06004836A (es) | 2003-11-05 | 2006-07-06 | Glycart Biotechnology Ag | Anticuerpos cd20 con funcion del efector y afinidad de enlace al receptor fc mejoradas. |
UY30003A1 (es) * | 2005-12-12 | 2007-08-31 | Hoffmann La Roche | Anticuerpos glicosilados en la region variable |
DE102006013531A1 (de) * | 2006-03-24 | 2007-09-27 | Lts Lohmann Therapie-Systeme Ag | Polylactid-Nanopartikel |
CN102164960A (zh) * | 2008-09-26 | 2011-08-24 | 罗氏格黎卡特股份公司 | 双特异性抗-egfr/抗-igf-1r抗体 |
JP5501439B2 (ja) * | 2009-04-02 | 2014-05-21 | ロシュ グリクアート アクチェンゲゼルシャフト | 完全長抗体と単鎖Fabフラグメントとを含む多重特異的抗体 |
RU2663120C2 (ru) * | 2012-08-29 | 2018-08-01 | Ф.Хоффманн-Ля Рош Аг | Шаттл для гематоэнцефалического барьера |
-
2013
- 2013-08-26 RU RU2015111093A patent/RU2663120C2/ru active
- 2013-08-26 JP JP2015528977A patent/JP6219956B2/ja active Active
- 2013-08-26 CN CN201380042265.1A patent/CN104520329A/zh active Pending
- 2013-08-26 SG SG10201702702VA patent/SG10201702702VA/en unknown
- 2013-08-26 ES ES13756076T patent/ES2733324T3/es active Active
- 2013-08-26 RU RU2018127006A patent/RU2711552C2/ru active
- 2013-08-26 DK DK13756076.9T patent/DK2890712T3/da active
- 2013-08-26 EP EP13756076.9A patent/EP2890712B1/en active Active
- 2013-08-26 NZ NZ703585A patent/NZ703585A/en unknown
- 2013-08-26 KR KR20157004942A patent/KR20150039798A/ko active Application Filing
- 2013-08-26 SG SG11201500583PA patent/SG11201500583PA/en unknown
- 2013-08-26 MX MX2015002215A patent/MX367126B/es active IP Right Grant
- 2013-08-26 PL PL13756076T patent/PL2890712T3/pl unknown
- 2013-08-26 HU HUE13756076A patent/HUE045144T2/hu unknown
- 2013-08-26 AU AU2013307406A patent/AU2013307406B2/en active Active
- 2013-08-26 MY MYPI2015000168A patent/MY178542A/en unknown
- 2013-08-26 CN CN201810972126.3A patent/CN109053901A/zh active Pending
- 2013-08-26 LT LTEP13756076.9T patent/LT2890712T/lt unknown
- 2013-08-26 KR KR1020177009426A patent/KR101885044B1/ko not_active Application Discontinuation
- 2013-08-26 SI SI201331492T patent/SI2890712T1/sl unknown
- 2013-08-26 BR BR112015004512-0A patent/BR112015004512B1/pt active IP Right Grant
- 2013-08-26 EP EP17199410.6A patent/EP3315514A1/en active Pending
- 2013-08-26 WO PCT/EP2013/067595 patent/WO2014033074A1/en active Application Filing
- 2013-08-26 CA CA2879496A patent/CA2879496C/en active Active
- 2013-08-26 KR KR1020197030778A patent/KR20190121874A/ko not_active Application Discontinuation
- 2013-08-26 RS RS20190813A patent/RS58928B1/sr unknown
- 2013-08-26 PT PT13756076T patent/PT2890712T/pt unknown
- 2013-08-26 TR TR2019/09156T patent/TR201909156T4/tr unknown
- 2013-08-26 KR KR1020187021343A patent/KR102036262B1/ko active IP Right Grant
-
2015
- 2015-01-16 ZA ZA2015/00346A patent/ZA201500346B/en unknown
- 2015-02-02 IL IL237064A patent/IL237064A0/en active IP Right Grant
- 2015-02-02 US US14/611,964 patent/US20150322149A1/en not_active Abandoned
- 2015-02-19 MX MX2019006259A patent/MX2019006259A/es unknown
- 2015-06-25 HK HK15106064.1A patent/HK1205521A1/zh unknown
-
2017
- 2017-09-28 JP JP2017187722A patent/JP2018029602A/ja active Pending
-
2018
- 2018-05-15 AU AU2018203400A patent/AU2018203400B2/en active Active
- 2018-12-19 US US16/225,370 patent/US20190276530A1/en not_active Abandoned
-
2019
- 2019-06-26 HR HRP20191153TT patent/HRP20191153T1/hr unknown
- 2019-09-12 JP JP2019166422A patent/JP6889218B2/ja active Active
- 2019-12-20 RU RU2019142838A patent/RU2754794C2/ru active
-
2020
- 2020-07-31 AU AU2020210286A patent/AU2020210286A1/en not_active Abandoned
- 2020-11-22 IL IL278872A patent/IL278872A/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050147613A1 (en) * | 1999-06-16 | 2005-07-07 | Boston Biomedical Research Institute | Immunological control of beta-amyloid levels in vivo |
WO2012075037A1 (en) * | 2010-11-30 | 2012-06-07 | Genentech, Inc. | Low affinity blood brain barrier receptor antibodies and uses therefor |
US20120171120A1 (en) * | 2010-11-30 | 2012-07-05 | Genentech, Inc. | Low affinity blood brain barrier receptor antibodies and uses therefor |
Non-Patent Citations (5)
Title |
---|
BICKEL U等: "Delivery of peptides and proteins through the blood-brain barrier", 《ADV DRUG DELIV REV》 * |
BOADO RJ 等: "Engineering and expression of a chimeric transferrin receptor monoclonal antibody for blood-brain barrier delivery in the mouse", 《BIOTECHNOL BIOENG》 * |
TUCKER IG: "Bickel U", 《THER DELIV》 * |
全毅等: "药物透过血脑屏障靶向传递系统的研究", 《国际神经病学神经外科学杂志》 * |
杨媛 等: "受体介导的脑靶向药物递送系统研究进展", 《中国药学杂志》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110101847A (zh) * | 2019-05-23 | 2019-08-09 | 北京豪思生物科技有限公司 | 转铁蛋白的应用及包含转铁蛋白的组合物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2018203400B2 (en) | Blood brain barrier shuttle | |
CN103443125B (zh) | 低亲和力血脑屏障受体抗体及其用途 | |
CN108992668A (zh) | 用于提高血脑屏障转运的安全性的方法 | |
CN107207591A (zh) | 血脑屏障受体抗体及使用方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181221 |