JP2017510294A - 異種ポリペプチドを分泌させるための方法及び組成物 - Google Patents
異種ポリペプチドを分泌させるための方法及び組成物 Download PDFInfo
- Publication number
- JP2017510294A JP2017510294A JP2016575644A JP2016575644A JP2017510294A JP 2017510294 A JP2017510294 A JP 2017510294A JP 2016575644 A JP2016575644 A JP 2016575644A JP 2016575644 A JP2016575644 A JP 2016575644A JP 2017510294 A JP2017510294 A JP 2017510294A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- signal peptide
- polynucleotide
- polypeptide
- sequence
- 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.)
- Granted
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 320
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 293
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 291
- 230000003248 secreting effect Effects 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims description 135
- 239000000203 mixture Substances 0.000 title claims description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 claims abstract description 432
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 85
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 73
- 102000040430 polynucleotide Human genes 0.000 claims description 193
- 108091033319 polynucleotide Proteins 0.000 claims description 193
- 239000002157 polynucleotide Substances 0.000 claims description 193
- 210000004027 cell Anatomy 0.000 claims description 131
- 241000282414 Homo sapiens Species 0.000 claims description 85
- 241000588724 Escherichia coli Species 0.000 claims description 55
- -1 tac Proteins 0.000 claims description 48
- 150000007523 nucleic acids Chemical class 0.000 claims description 41
- 102000039446 nucleic acids Human genes 0.000 claims description 40
- 108020004707 nucleic acids Proteins 0.000 claims description 40
- 230000001965 increasing effect Effects 0.000 claims description 34
- 238000004519 manufacturing process Methods 0.000 claims description 34
- 230000035772 mutation Effects 0.000 claims description 33
- 230000028327 secretion Effects 0.000 claims description 31
- 239000013598 vector Substances 0.000 claims description 30
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 29
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 29
- 230000014509 gene expression Effects 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 25
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 claims description 24
- 102000005962 receptors Human genes 0.000 claims description 23
- 108060003951 Immunoglobulin Proteins 0.000 claims description 19
- 102000018358 immunoglobulin Human genes 0.000 claims description 19
- 239000013604 expression vector Substances 0.000 claims description 14
- 102220558029 Glutathione hydrolase 5 proenzyme_L11I_mutation Human genes 0.000 claims description 12
- 238000012258 culturing Methods 0.000 claims description 11
- 101150009573 phoA gene Proteins 0.000 claims description 11
- 102220054627 rs45495192 Human genes 0.000 claims description 11
- 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 claims description 10
- 239000004365 Protease Substances 0.000 claims description 8
- 108091005804 Peptidases Proteins 0.000 claims description 7
- 102220479740 Cell division cycle protein 123 homolog_S11I_mutation Human genes 0.000 claims description 6
- 108010006519 Molecular Chaperones Proteins 0.000 claims description 6
- 102000005431 Molecular Chaperones Human genes 0.000 claims description 6
- 238000004113 cell culture Methods 0.000 claims description 6
- 102200158393 rs5030732 Human genes 0.000 claims description 6
- 239000006143 cell culture medium Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 5
- 101150081864 Spr gene Proteins 0.000 claims description 4
- 230000002950 deficient Effects 0.000 claims description 4
- 101150018266 degP gene Proteins 0.000 claims description 4
- 101150036535 prc gene Proteins 0.000 claims description 4
- 102200048773 rs2224391 Human genes 0.000 claims description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 3
- 241000894006 Bacteria Species 0.000 abstract description 10
- 125000003275 alpha amino acid group Chemical group 0.000 description 78
- 239000000427 antigen Substances 0.000 description 67
- 206010028980 Neoplasm Diseases 0.000 description 66
- 230000027455 binding Effects 0.000 description 66
- 108091007433 antigens Proteins 0.000 description 64
- 102000036639 antigens Human genes 0.000 description 64
- 235000018102 proteins Nutrition 0.000 description 58
- 230000014616 translation Effects 0.000 description 56
- 238000013519 translation Methods 0.000 description 55
- 125000000539 amino acid group Chemical group 0.000 description 43
- 238000001262 western blot Methods 0.000 description 41
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 39
- 235000001014 amino acid Nutrition 0.000 description 38
- 201000011510 cancer Diseases 0.000 description 38
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 35
- 230000002829 reductive effect Effects 0.000 description 31
- 238000006467 substitution reaction Methods 0.000 description 31
- 229940024606 amino acid Drugs 0.000 description 27
- 150000001413 amino acids Chemical class 0.000 description 27
- 239000012634 fragment Substances 0.000 description 25
- 239000000523 sample Substances 0.000 description 25
- 239000003814 drug Substances 0.000 description 22
- 108020003175 receptors Proteins 0.000 description 22
- 241000894007 species Species 0.000 description 22
- 208000035475 disorder Diseases 0.000 description 21
- 230000004048 modification Effects 0.000 description 21
- 238000012986 modification Methods 0.000 description 21
- 102000003816 Interleukin-13 Human genes 0.000 description 20
- 108090000176 Interleukin-13 Proteins 0.000 description 20
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 18
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 18
- 210000001322 periplasm Anatomy 0.000 description 18
- 230000006870 function Effects 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 239000000499 gel Substances 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 229940002612 prodrug Drugs 0.000 description 15
- 239000000651 prodrug Substances 0.000 description 15
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 14
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 14
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 14
- 239000004473 Threonine Substances 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 230000001976 improved effect Effects 0.000 description 14
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 13
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 13
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 229940127089 cytotoxic agent Drugs 0.000 description 12
- 108020004705 Codon Proteins 0.000 description 11
- 108010000499 Thromboplastin Proteins 0.000 description 11
- 102100030859 Tissue factor Human genes 0.000 description 11
- 238000013459 approach Methods 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 239000002246 antineoplastic agent Substances 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
- 238000011144 upstream manufacturing Methods 0.000 description 10
- 102220574842 Gap junction alpha-3 protein_L11S_mutation Human genes 0.000 description 9
- 108010071390 Serum Albumin Proteins 0.000 description 9
- 102000007562 Serum Albumin Human genes 0.000 description 9
- 235000004279 alanine Nutrition 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 210000004899 c-terminal region Anatomy 0.000 description 9
- 230000014621 translational initiation Effects 0.000 description 9
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 9
- 102100036302 C-C chemokine receptor type 6 Human genes 0.000 description 8
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 8
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 108700039208 TraU Proteins 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 235000018417 cysteine Nutrition 0.000 description 8
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 8
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 8
- 238000003752 polymerase chain reaction Methods 0.000 description 8
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 8
- 108700012359 toxins Proteins 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 7
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 7
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 7
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 7
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 7
- 102000004388 Interleukin-4 Human genes 0.000 description 7
- 108090000978 Interleukin-4 Proteins 0.000 description 7
- 108010025020 Nerve Growth Factor Proteins 0.000 description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
- 102000046283 TNF-Related Apoptosis-Inducing Ligand Human genes 0.000 description 7
- 108700012411 TNFSF10 Proteins 0.000 description 7
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000001363 autoimmune Effects 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000010494 dissociation reaction Methods 0.000 description 7
- 230000005593 dissociations Effects 0.000 description 7
- 239000012636 effector Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 230000008676 import Effects 0.000 description 7
- 150000002482 oligosaccharides Chemical class 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 239000003053 toxin Substances 0.000 description 7
- 231100000765 toxin Toxicity 0.000 description 7
- 102100036846 C-C motif chemokine 21 Human genes 0.000 description 6
- 102100036849 C-C motif chemokine 24 Human genes 0.000 description 6
- 102100021936 C-C motif chemokine 27 Human genes 0.000 description 6
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 6
- 102100025618 C-X-C chemokine receptor type 6 Human genes 0.000 description 6
- 101150013553 CD40 gene Proteins 0.000 description 6
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 6
- 229940045513 CTLA4 antagonist Drugs 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 6
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 6
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 6
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 6
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 6
- 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 description 6
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 6
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 6
- 102100039064 Interleukin-3 Human genes 0.000 description 6
- 102000004890 Interleukin-8 Human genes 0.000 description 6
- 108090001007 Interleukin-8 Proteins 0.000 description 6
- 102000015696 Interleukins Human genes 0.000 description 6
- 108010063738 Interleukins Proteins 0.000 description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- 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 6
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 6
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 6
- 108090000099 Neurotrophin-4 Proteins 0.000 description 6
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 6
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 6
- 108010009583 Transforming Growth Factors Proteins 0.000 description 6
- 102000009618 Transforming Growth Factors Human genes 0.000 description 6
- 239000007997 Tricine buffer Substances 0.000 description 6
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 229940127121 immunoconjugate Drugs 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000002703 mutagenesis Methods 0.000 description 6
- 231100000350 mutagenesis Toxicity 0.000 description 6
- 229920001542 oligosaccharide Polymers 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000002062 proliferating effect Effects 0.000 description 6
- 238000011321 prophylaxis Methods 0.000 description 6
- 230000002285 radioactive effect Effects 0.000 description 6
- 238000013207 serial dilution Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 6
- 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 6
- 210000001519 tissue Anatomy 0.000 description 6
- 239000004474 valine Substances 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 5
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 5
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 5
- 102100032937 CD40 ligand Human genes 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 5
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 5
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 5
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 108091006905 Human Serum Albumin Proteins 0.000 description 5
- 102000008100 Human Serum Albumin Human genes 0.000 description 5
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 5
- 102000003814 Interleukin-10 Human genes 0.000 description 5
- 108090000174 Interleukin-10 Proteins 0.000 description 5
- 102000013462 Interleukin-12 Human genes 0.000 description 5
- 108010065805 Interleukin-12 Proteins 0.000 description 5
- 102100033461 Interleukin-17A Human genes 0.000 description 5
- 102000003810 Interleukin-18 Human genes 0.000 description 5
- 108090000171 Interleukin-18 Proteins 0.000 description 5
- 108010002616 Interleukin-5 Proteins 0.000 description 5
- 102000000743 Interleukin-5 Human genes 0.000 description 5
- 108010002335 Interleukin-9 Proteins 0.000 description 5
- 102000000585 Interleukin-9 Human genes 0.000 description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- 102000016267 Leptin Human genes 0.000 description 5
- 108010092277 Leptin Proteins 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 5
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 5
- 102100036011 T-cell surface glycoprotein CD4 Human genes 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
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 5
- 239000000562 conjugate Substances 0.000 description 5
- 239000002254 cytotoxic agent Substances 0.000 description 5
- 231100000599 cytotoxic agent Toxicity 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 230000016784 immunoglobulin production Effects 0.000 description 5
- 210000003000 inclusion body Anatomy 0.000 description 5
- 229940039781 leptin Drugs 0.000 description 5
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 238000002823 phage display Methods 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 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 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 101150065732 tir gene Proteins 0.000 description 5
- 229960005486 vaccine Drugs 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 4
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 4
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 4
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 4
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 4
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 4
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 4
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 4
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 4
- 102100023700 C-C motif chemokine 16 Human genes 0.000 description 4
- 102100023701 C-C motif chemokine 18 Human genes 0.000 description 4
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 4
- 102100036848 C-C motif chemokine 20 Human genes 0.000 description 4
- 102100021933 C-C motif chemokine 25 Human genes 0.000 description 4
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 4
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 4
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 4
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 4
- 102100036153 C-X-C motif chemokine 6 Human genes 0.000 description 4
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 4
- 108010029697 CD40 Ligand Proteins 0.000 description 4
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 108010054218 Factor VIII Proteins 0.000 description 4
- 102000001690 Factor VIII Human genes 0.000 description 4
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 4
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 4
- 102100028417 Fibroblast growth factor 12 Human genes 0.000 description 4
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 4
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 4
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 4
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 4
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 4
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 4
- 101000978375 Homo sapiens C-C motif chemokine 16 Proteins 0.000 description 4
- 101000978371 Homo sapiens C-C motif chemokine 18 Proteins 0.000 description 4
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 4
- 101000713078 Homo sapiens C-C motif chemokine 24 Proteins 0.000 description 4
- 101000897486 Homo sapiens C-C motif chemokine 25 Proteins 0.000 description 4
- 101000897494 Homo sapiens C-C motif chemokine 27 Proteins 0.000 description 4
- 101000916059 Homo sapiens C-X-C chemokine receptor type 2 Proteins 0.000 description 4
- 101000856683 Homo sapiens C-X-C chemokine receptor type 6 Proteins 0.000 description 4
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 4
- 101000917234 Homo sapiens Fibroblast growth factor 12 Proteins 0.000 description 4
- 101000843810 Homo sapiens Hydroxycarboxylic acid receptor 1 Proteins 0.000 description 4
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 description 4
- 101001017968 Homo sapiens Leukotriene B4 receptor 1 Proteins 0.000 description 4
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 description 4
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 4
- 102100030642 Hydroxycarboxylic acid receptor 1 Human genes 0.000 description 4
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 4
- 108010047761 Interferon-alpha Proteins 0.000 description 4
- 102000006992 Interferon-alpha Human genes 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000003777 Interleukin-1 beta Human genes 0.000 description 4
- 108090000193 Interleukin-1 beta Proteins 0.000 description 4
- 102100033101 Interleukin-17B Human genes 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 102100036678 Interleukin-27 subunit alpha Human genes 0.000 description 4
- 108010002386 Interleukin-3 Proteins 0.000 description 4
- 108090001005 Interleukin-6 Proteins 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- 102100033374 Leukotriene B4 receptor 1 Human genes 0.000 description 4
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 4
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 4
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 108090000742 Neurotrophin 3 Proteins 0.000 description 4
- 102100029268 Neurotrophin-3 Human genes 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108010090127 Periplasmic Proteins Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 102000014128 RANK Ligand Human genes 0.000 description 4
- 108010025832 RANK Ligand Proteins 0.000 description 4
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 4
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 4
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 4
- 102000012883 Tumor Necrosis Factor Ligand Superfamily Member 14 Human genes 0.000 description 4
- 108010065158 Tumor Necrosis Factor Ligand Superfamily Member 14 Proteins 0.000 description 4
- 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 description 4
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 4
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 4
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 4
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000488 activin Substances 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000000611 antibody drug conjugate Substances 0.000 description 4
- 229940049595 antibody-drug conjugate Drugs 0.000 description 4
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 235000008191 folinic acid Nutrition 0.000 description 4
- 239000011672 folinic acid Substances 0.000 description 4
- 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 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 229910052737 gold Inorganic materials 0.000 description 4
- 239000010931 gold Substances 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 239000000122 growth hormone Substances 0.000 description 4
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000893 inhibin Substances 0.000 description 4
- 102000006495 integrins Human genes 0.000 description 4
- 108010044426 integrins Proteins 0.000 description 4
- 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 4
- 229960001691 leucovorin Drugs 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- 210000004897 n-terminal region Anatomy 0.000 description 4
- 229940053128 nerve growth factor Drugs 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 239000012130 whole-cell lysate Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 108010059616 Activins Proteins 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 3
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 3
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 3
- 102100023698 C-C motif chemokine 17 Human genes 0.000 description 3
- 102100036842 C-C motif chemokine 19 Human genes 0.000 description 3
- 102100036850 C-C motif chemokine 23 Human genes 0.000 description 3
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 3
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 3
- 102100025279 C-X-C motif chemokine 11 Human genes 0.000 description 3
- 102100025221 CD70 antigen Human genes 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108010055166 Chemokine CCL5 Proteins 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 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 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- 108090000204 Dipeptidase 1 Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010039471 Fas Ligand Protein Proteins 0.000 description 3
- 102100035307 Fibroblast growth factor 16 Human genes 0.000 description 3
- 108050002072 Fibroblast growth factor 16 Proteins 0.000 description 3
- 102100031734 Fibroblast growth factor 19 Human genes 0.000 description 3
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 3
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 3
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 3
- 101000978362 Homo sapiens C-C motif chemokine 17 Proteins 0.000 description 3
- 101000713106 Homo sapiens C-C motif chemokine 19 Proteins 0.000 description 3
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 3
- 101000713081 Homo sapiens C-C motif chemokine 23 Proteins 0.000 description 3
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 3
- 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 3
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 3
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 3
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 3
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 description 3
- 101000852998 Homo sapiens Interleukin-27 subunit alpha Proteins 0.000 description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 3
- 101000764535 Homo sapiens Lymphotoxin-alpha Proteins 0.000 description 3
- 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 3
- 102000026633 IL6 Human genes 0.000 description 3
- 102100026818 Inhibin beta E chain Human genes 0.000 description 3
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 3
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 3
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 3
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 3
- 102100025390 Integrin beta-2 Human genes 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 3
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 3
- 108090000177 Interleukin-11 Proteins 0.000 description 3
- 102000003815 Interleukin-11 Human genes 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 102000003812 Interleukin-15 Human genes 0.000 description 3
- 102100039879 Interleukin-19 Human genes 0.000 description 3
- 102000013264 Interleukin-23 Human genes 0.000 description 3
- 108010065637 Interleukin-23 Proteins 0.000 description 3
- 102100036680 Interleukin-25 Human genes 0.000 description 3
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 3
- 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 3
- 102100026238 Lymphotoxin-alpha Human genes 0.000 description 3
- 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 3
- 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 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 102000003683 Neurotrophin-4 Human genes 0.000 description 3
- 102100033857 Neurotrophin-4 Human genes 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 3
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 3
- 102000036693 Thrombopoietin Human genes 0.000 description 3
- 108010041111 Thrombopoietin Proteins 0.000 description 3
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 3
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 3
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 3
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 3
- 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 3
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 3
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 3
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 3
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 3
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 229940112869 bone morphogenetic protein Drugs 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin 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-LULTVBGHSA-N 0.000 description 3
- 229930195731 calicheamicin Natural products 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 229940044683 chemotherapy drug Drugs 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 230000000593 degrading effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 238000002825 functional assay Methods 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000003966 growth inhibitor Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 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 3
- 238000002156 mixing Methods 0.000 description 3
- 230000000683 nonmetastatic effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 238000000734 protein sequencing Methods 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 239000012723 sample buffer Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 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 description 3
- 230000003612 virological effect Effects 0.000 description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 2
- 102100036933 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor Human genes 0.000 description 2
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical class NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VPFUWHKTPYPNGT-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)propan-1-one Chemical compound OC1=C2C=CC(C)(C)OC2=CC=C1C(=O)CCC1=CC=C(O)C(O)=C1 VPFUWHKTPYPNGT-UHFFFAOYSA-N 0.000 description 2
- QXZBMSIDSOZZHK-DOPDSADYSA-N 31362-50-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CNC=N1 QXZBMSIDSOZZHK-DOPDSADYSA-N 0.000 description 2
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 description 2
- 108010082808 4-1BB Ligand Proteins 0.000 description 2
- 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 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
- 101710151993 Amyloid-beta precursor protein Proteins 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
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 2
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 2
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 2
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 2
- 108010051479 Bombesin Proteins 0.000 description 2
- 102000013585 Bombesin Human genes 0.000 description 2
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 2
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 2
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 2
- 102100022545 Bone morphogenetic protein 8B Human genes 0.000 description 2
- 102100031174 C-C chemokine receptor type 10 Human genes 0.000 description 2
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 2
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
- 102100036303 C-C chemokine receptor type 9 Human genes 0.000 description 2
- 101710112613 C-C motif chemokine 13 Proteins 0.000 description 2
- 102100023703 C-C motif chemokine 15 Human genes 0.000 description 2
- 101710112538 C-C motif chemokine 27 Proteins 0.000 description 2
- 102100021942 C-C motif chemokine 28 Human genes 0.000 description 2
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 2
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 2
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 2
- 102100025250 C-X-C motif chemokine 14 Human genes 0.000 description 2
- 102100039396 C-X-C motif chemokine 16 Human genes 0.000 description 2
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 2
- 102100036189 C-X-C motif chemokine 3 Human genes 0.000 description 2
- 101710085504 C-X-C motif chemokine 6 Proteins 0.000 description 2
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 2
- 102100032957 C5a anaphylatoxin chemotactic receptor 1 Human genes 0.000 description 2
- 108010009575 CD55 Antigens Proteins 0.000 description 2
- 102100040531 CKLF-like MARVEL transmembrane domain-containing protein 2 Human genes 0.000 description 2
- 102100040527 CKLF-like MARVEL transmembrane domain-containing protein 3 Human genes 0.000 description 2
- 102100040529 CKLF-like MARVEL transmembrane domain-containing protein 4 Human genes 0.000 description 2
- 102100040525 CKLF-like MARVEL transmembrane domain-containing protein 5 Human genes 0.000 description 2
- 102100040528 CKLF-like MARVEL transmembrane domain-containing protein 6 Human genes 0.000 description 2
- 102100040855 CKLF-like MARVEL transmembrane domain-containing protein 7 Human genes 0.000 description 2
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 2
- 108010061304 CXCR6 Receptors Proteins 0.000 description 2
- 102100022480 Cadherin-20 Human genes 0.000 description 2
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 2
- 102400000113 Calcitonin Human genes 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- 101001110283 Canis lupus familiaris Ras-related C3 botulinum toxin substrate 1 Proteins 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
- 201000009030 Carcinoma Diseases 0.000 description 2
- 102100028892 Cardiotrophin-1 Human genes 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 2
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 2
- 108010083647 Chemokine CCL24 Proteins 0.000 description 2
- 108010083698 Chemokine CCL26 Proteins 0.000 description 2
- 102100022641 Coagulation factor IX Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 102100036329 Cyclin-dependent kinase 3 Human genes 0.000 description 2
- 108010025880 Cyclomaltodextrin glucanotransferase Proteins 0.000 description 2
- 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 2
- 102100035298 Cytokine SCM-1 beta Human genes 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 108010049207 Death Domain Receptors Proteins 0.000 description 2
- 102000009058 Death Domain Receptors Human genes 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102100020743 Dipeptidase 1 Human genes 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102100023688 Eotaxin Human genes 0.000 description 2
- 101710139422 Eotaxin Proteins 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 102100031939 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 108010076282 Factor IX Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 2
- 102100028413 Fibroblast growth factor 11 Human genes 0.000 description 2
- 102100035292 Fibroblast growth factor 14 Human genes 0.000 description 2
- 102100035308 Fibroblast growth factor 17 Human genes 0.000 description 2
- 102100031361 Fibroblast growth factor 20 Human genes 0.000 description 2
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 2
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 2
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 description 2
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 description 2
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 2
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 2
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 2
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- 102100020997 Fractalkine Human genes 0.000 description 2
- 101150019176 GDF10 gene Proteins 0.000 description 2
- 101710115997 Gamma-tubulin complex component 2 Proteins 0.000 description 2
- 102400000321 Glucagon Human genes 0.000 description 2
- 108060003199 Glucagon Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 108010051696 Growth Hormone Proteins 0.000 description 2
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 2
- 102100040895 Growth/differentiation factor 10 Human genes 0.000 description 2
- 102100035379 Growth/differentiation factor 5 Human genes 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101001071349 Homo sapiens 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor Proteins 0.000 description 2
- 101000798902 Homo sapiens Atypical chemokine receptor 4 Proteins 0.000 description 2
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 2
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 2
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 2
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 description 2
- 101000899368 Homo sapiens Bone morphogenetic protein 8B Proteins 0.000 description 2
- 101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 2
- 101000980744 Homo sapiens C-C chemokine receptor type 3 Proteins 0.000 description 2
- 101000738584 Homo sapiens C-C chemokine receptor type 4 Proteins 0.000 description 2
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 2
- 101000978379 Homo sapiens C-C motif chemokine 13 Proteins 0.000 description 2
- 101000978376 Homo sapiens C-C motif chemokine 15 Proteins 0.000 description 2
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 2
- 101000897477 Homo sapiens C-C motif chemokine 28 Proteins 0.000 description 2
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 2
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 description 2
- 101000946794 Homo sapiens C-C motif chemokine 8 Proteins 0.000 description 2
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 2
- 101000858060 Homo sapiens C-X-C motif chemokine 11 Proteins 0.000 description 2
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 2
- 101000858068 Homo sapiens C-X-C motif chemokine 14 Proteins 0.000 description 2
- 101000889133 Homo sapiens C-X-C motif chemokine 16 Proteins 0.000 description 2
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 2
- 101000947193 Homo sapiens C-X-C motif chemokine 3 Proteins 0.000 description 2
- 101000947177 Homo sapiens C-X-C motif chemokine 6 Proteins 0.000 description 2
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 description 2
- 101000867983 Homo sapiens C5a anaphylatoxin chemotactic receptor 1 Proteins 0.000 description 2
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 2
- 101000749427 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 2 Proteins 0.000 description 2
- 101000749433 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 3 Proteins 0.000 description 2
- 101000749431 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 4 Proteins 0.000 description 2
- 101000749437 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 5 Proteins 0.000 description 2
- 101000749435 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 6 Proteins 0.000 description 2
- 101000749308 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 7 Proteins 0.000 description 2
- 101000899459 Homo sapiens Cadherin-20 Proteins 0.000 description 2
- 101000715946 Homo sapiens Cyclin-dependent kinase 3 Proteins 0.000 description 2
- 101000804771 Homo sapiens Cytokine SCM-1 beta Proteins 0.000 description 2
- 101000917237 Homo sapiens Fibroblast growth factor 10 Proteins 0.000 description 2
- 101000917236 Homo sapiens Fibroblast growth factor 11 Proteins 0.000 description 2
- 101000878181 Homo sapiens Fibroblast growth factor 14 Proteins 0.000 description 2
- 101000846532 Homo sapiens Fibroblast growth factor 20 Proteins 0.000 description 2
- 101001051973 Homo sapiens Fibroblast growth factor 23 Proteins 0.000 description 2
- 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 description 2
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 description 2
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 description 2
- 101001060265 Homo sapiens Fibroblast growth factor 6 Proteins 0.000 description 2
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 2
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 description 2
- 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- 101001023988 Homo sapiens Growth/differentiation factor 5 Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101000959794 Homo sapiens Interferon alpha-2 Proteins 0.000 description 2
- 101000959708 Homo sapiens Interferon alpha-4 Proteins 0.000 description 2
- 101000959704 Homo sapiens Interferon alpha-5 Proteins 0.000 description 2
- 101000959714 Homo sapiens Interferon alpha-6 Proteins 0.000 description 2
- 101000961126 Homo sapiens Interferon alpha-7 Proteins 0.000 description 2
- 101001002466 Homo sapiens Interferon lambda-3 Proteins 0.000 description 2
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 2
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 2
- 101000960952 Homo sapiens Interleukin-1 receptor accessory protein Proteins 0.000 description 2
- 101000994815 Homo sapiens Interleukin-1 receptor accessory protein-like 1 Proteins 0.000 description 2
- 101001076422 Homo sapiens Interleukin-1 receptor type 2 Proteins 0.000 description 2
- 101000852965 Homo sapiens Interleukin-1 receptor-like 2 Proteins 0.000 description 2
- 101001003142 Homo sapiens Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 2
- 101001003138 Homo sapiens Interleukin-12 receptor subunit beta-2 Proteins 0.000 description 2
- 101001010600 Homo sapiens Interleukin-12 subunit alpha Proteins 0.000 description 2
- 101000852992 Homo sapiens Interleukin-12 subunit beta Proteins 0.000 description 2
- 101001003135 Homo sapiens Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 2
- 101001003132 Homo sapiens Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 2
- 101001003140 Homo sapiens Interleukin-15 receptor subunit alpha Proteins 0.000 description 2
- 101001019598 Homo sapiens Interleukin-17 receptor A Proteins 0.000 description 2
- 101001019615 Homo sapiens Interleukin-18 receptor accessory protein Proteins 0.000 description 2
- 101001019591 Homo sapiens Interleukin-18-binding protein Proteins 0.000 description 2
- 101000960946 Homo sapiens Interleukin-19 Proteins 0.000 description 2
- 101001010591 Homo sapiens Interleukin-20 Proteins 0.000 description 2
- 101001044893 Homo sapiens Interleukin-20 receptor subunit alpha Proteins 0.000 description 2
- 101001044883 Homo sapiens Interleukin-22 receptor subunit alpha-1 Proteins 0.000 description 2
- 101001044887 Homo sapiens Interleukin-22 receptor subunit alpha-2 Proteins 0.000 description 2
- 101000853009 Homo sapiens Interleukin-24 Proteins 0.000 description 2
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 description 2
- 101001033279 Homo sapiens Interleukin-3 Proteins 0.000 description 2
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 2
- 101001040964 Homo sapiens Interleukin-36 receptor antagonist protein Proteins 0.000 description 2
- 101001033312 Homo sapiens Interleukin-4 receptor subunit alpha Proteins 0.000 description 2
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 description 2
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 2
- 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 2
- 101000582950 Homo sapiens Platelet factor 4 Proteins 0.000 description 2
- 101000655540 Homo sapiens Protransforming growth factor alpha Proteins 0.000 description 2
- 101000668165 Homo sapiens RNA-binding motif, single-stranded-interacting protein 1 Proteins 0.000 description 2
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 2
- 101000684994 Homo sapiens Stromal cell-derived factor 2 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- 101000635958 Homo sapiens Transforming growth factor beta-2 proprotein Proteins 0.000 description 2
- 101000894525 Homo sapiens Transforming growth factor-beta-induced protein ig-h3 Proteins 0.000 description 2
- 101000830598 Homo sapiens Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 2
- 101000830600 Homo sapiens Tumor necrosis factor ligand superfamily member 13 Proteins 0.000 description 2
- 101000830596 Homo sapiens Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 2
- 101000638255 Homo sapiens Tumor necrosis factor ligand superfamily member 8 Proteins 0.000 description 2
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 2
- 101000742579 Homo sapiens Vascular endothelial growth factor B Proteins 0.000 description 2
- 101000742596 Homo sapiens Vascular endothelial growth factor C Proteins 0.000 description 2
- 101000742599 Homo sapiens Vascular endothelial growth factor D Proteins 0.000 description 2
- 101000994810 Homo sapiens X-linked interleukin-1 receptor accessory protein-like 2 Proteins 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 108091058560 IL8 Proteins 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 108010041012 Integrin alpha4 Proteins 0.000 description 2
- 102000008607 Integrin beta3 Human genes 0.000 description 2
- 108010020950 Integrin beta3 Proteins 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 102100039949 Interferon alpha-4 Human genes 0.000 description 2
- 102100039948 Interferon alpha-5 Human genes 0.000 description 2
- 102100040007 Interferon alpha-6 Human genes 0.000 description 2
- 102100039350 Interferon alpha-7 Human genes 0.000 description 2
- 102100020992 Interferon lambda-3 Human genes 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 102000003996 Interferon-beta Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 108700003107 Interleukin-1 Receptor-Like 1 Proteins 0.000 description 2
- 102100039065 Interleukin-1 beta Human genes 0.000 description 2
- 102100039880 Interleukin-1 receptor accessory protein Human genes 0.000 description 2
- 102100034413 Interleukin-1 receptor accessory protein-like 1 Human genes 0.000 description 2
- 102100026017 Interleukin-1 receptor type 2 Human genes 0.000 description 2
- 102100036706 Interleukin-1 receptor-like 1 Human genes 0.000 description 2
- 102100036697 Interleukin-1 receptor-like 2 Human genes 0.000 description 2
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 2
- 102100020792 Interleukin-12 receptor subunit beta-2 Human genes 0.000 description 2
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 2
- 102100036701 Interleukin-12 subunit beta Human genes 0.000 description 2
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 2
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 2
- 102100020789 Interleukin-15 receptor subunit alpha Human genes 0.000 description 2
- 101800003050 Interleukin-16 Proteins 0.000 description 2
- 102000049772 Interleukin-16 Human genes 0.000 description 2
- 102100035018 Interleukin-17 receptor A Human genes 0.000 description 2
- 102100035010 Interleukin-18 receptor accessory protein Human genes 0.000 description 2
- 102100035017 Interleukin-18-binding protein Human genes 0.000 description 2
- 102100022706 Interleukin-20 receptor subunit alpha Human genes 0.000 description 2
- 108010017411 Interleukin-21 Receptors Proteins 0.000 description 2
- 102100030699 Interleukin-21 receptor Human genes 0.000 description 2
- 102100030703 Interleukin-22 Human genes 0.000 description 2
- 102100022723 Interleukin-22 receptor subunit alpha-1 Human genes 0.000 description 2
- 102100022703 Interleukin-22 receptor subunit alpha-2 Human genes 0.000 description 2
- 102100036671 Interleukin-24 Human genes 0.000 description 2
- 102100036679 Interleukin-26 Human genes 0.000 description 2
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 2
- 102100021150 Interleukin-36 receptor antagonist protein Human genes 0.000 description 2
- 102100039078 Interleukin-4 receptor subunit alpha Human genes 0.000 description 2
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 101001089108 Lotus tetragonolobus Anti-H(O) lectin Proteins 0.000 description 2
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 2
- 102100035304 Lymphotactin Human genes 0.000 description 2
- 102100037267 Mammaglobin-B Human genes 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102100030335 Midkine Human genes 0.000 description 2
- 101100005657 Mus musculus Ccr7 gene Proteins 0.000 description 2
- 101100446506 Mus musculus Fgf3 gene Proteins 0.000 description 2
- 101100027996 Mus musculus Omg gene Proteins 0.000 description 2
- 101100178822 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) htrA1 gene Proteins 0.000 description 2
- 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 2
- 108090000028 Neprilysin Proteins 0.000 description 2
- 102000003729 Neprilysin Human genes 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 108090000445 Parathyroid hormone Proteins 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 102100036154 Platelet basic protein Human genes 0.000 description 2
- 102100030304 Platelet factor 4 Human genes 0.000 description 2
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 2
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 108010076181 Proinsulin Proteins 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 101800004937 Protein C Proteins 0.000 description 2
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 2
- 101710109947 Protein kinase C alpha type Proteins 0.000 description 2
- 108010019674 Proto-Oncogene Proteins c-sis Proteins 0.000 description 2
- 102100032350 Protransforming growth factor alpha Human genes 0.000 description 2
- 101710148333 Regulator of G-protein signaling 13 Proteins 0.000 description 2
- 102100021035 Regulator of G-protein signaling 18 Human genes 0.000 description 2
- 102100037415 Regulator of G-protein signaling 3 Human genes 0.000 description 2
- 101710140411 Regulator of G-protein signaling 3 Proteins 0.000 description 2
- 102400000834 Relaxin A chain Human genes 0.000 description 2
- 101800000074 Relaxin A chain Proteins 0.000 description 2
- 102400000610 Relaxin B chain Human genes 0.000 description 2
- 101710109558 Relaxin B chain Proteins 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- 101100277437 Rhizobium meliloti (strain 1021) degP1 gene Proteins 0.000 description 2
- 102400000827 Saposin-D Human genes 0.000 description 2
- 101800001700 Saposin-D Proteins 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 102100022831 Somatoliberin Human genes 0.000 description 2
- 101710142969 Somatoliberin Proteins 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- 102100038803 Somatotropin Human genes 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 2
- 102100023184 Stromal cell-derived factor 2 Human genes 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 description 2
- 206010042953 Systemic sclerosis Diseases 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 102100034195 Thrombopoietin Human genes 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 2
- 101710183280 Topoisomerase Proteins 0.000 description 2
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 102100030737 Transforming growth factor beta-2 proprotein Human genes 0.000 description 2
- 102100021398 Transforming growth factor-beta-induced protein ig-h3 Human genes 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 101710097155 Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 2
- 102100024585 Tumor necrosis factor ligand superfamily member 13 Human genes 0.000 description 2
- 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 description 2
- 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 description 2
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 2
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 2
- 102100034412 X-linked interleukin-1 receptor accessory protein-like 2 Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products 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 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 2
- 229960003437 aminoglutethimide Drugs 0.000 description 2
- 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 description 2
- 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 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- KMGARVOVYXNAOF-UHFFFAOYSA-N benzpiperylone Chemical compound C1CN(C)CCC1N1C(=O)C(CC=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 KMGARVOVYXNAOF-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 201000000053 blastoma Diseases 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)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=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
- 229960004015 calcitonin Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 108010041776 cardiotrophin 1 Proteins 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
- 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
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 2
- 229950001725 carubicin Drugs 0.000 description 2
- 238000012219 cassette mutagenesis Methods 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 230000001447 compensatory effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 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 2
- 238000001212 derivatisation Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- FOCAHLGSDWHSAH-UHFFFAOYSA-N difluoromethanethione Chemical compound FC(F)=S FOCAHLGSDWHSAH-UHFFFAOYSA-N 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
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- CTSPAMFJBXKSOY-UHFFFAOYSA-N ellipticine Chemical compound N1=CC=C2C(C)=C(NC=3C4=CC=CC=3)C4=C(C)C2=C1 CTSPAMFJBXKSOY-UHFFFAOYSA-N 0.000 description 2
- 201000008184 embryoma Diseases 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 229960004222 factor ix Drugs 0.000 description 2
- 229960000301 factor viii Drugs 0.000 description 2
- 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 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 230000033581 fucosylation Effects 0.000 description 2
- 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 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 2
- 229960004666 glucagon Drugs 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000002637 immunotoxin Effects 0.000 description 2
- 229940051026 immunotoxin Drugs 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 231100000608 immunotoxin Toxicity 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 230000002608 insulinlike Effects 0.000 description 2
- 108010021315 integrin beta7 Proteins 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 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
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000003580 lung surfactant Substances 0.000 description 2
- 108010019677 lymphotactin Proteins 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 2
- 229960004961 mechlorethamine Drugs 0.000 description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
- 229960001428 mercaptopurine Drugs 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 229960001156 mitoxantrone Drugs 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 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 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 229960001319 parathyroid hormone Drugs 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108010087851 prorelaxin Proteins 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 229960000856 protein c Drugs 0.000 description 2
- 231100000654 protein toxin Toxicity 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 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 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 229960001196 thiotepa Drugs 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- 229940113038 tnkase Drugs 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- LZAJKCZTKKKZNT-PMNGPLLRSA-N trichothecene Chemical compound C12([C@@]3(CC[C@H]2OC2C=C(CCC23C)C)C)CO1 LZAJKCZTKKKZNT-PMNGPLLRSA-N 0.000 description 2
- 229930013292 trichothecene Natural products 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 108010087967 type I signal peptidase Proteins 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 229960005356 urokinase Drugs 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
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920003169 water-soluble polymer Polymers 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 1
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-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
- URLVCROWVOSNPT-XOTOMLERSA-N (2s)-4-[(13r)-13-hydroxy-13-[(2r,5r)-5-[(2r,5r)-5-[(1r)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@@H]([C@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-XOTOMLERSA-N 0.000 description 1
- 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 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-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 1
- 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 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
- 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 1
- 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 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- 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 1
- 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 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- LJJFNFYPZOHRHM-UHFFFAOYSA-N 1-isocyano-2-methoxy-2-methylpropane Chemical compound COC(C)(C)C[N+]#[C-] LJJFNFYPZOHRHM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- 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 1
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 1
- FBUTXZSKZCQABC-UHFFFAOYSA-N 2-amino-1-methyl-7h-purine-6-thione Chemical compound S=C1N(C)C(N)=NC2=C1NC=N2 FBUTXZSKZCQABC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AOPRXJXHLWYPQR-UHFFFAOYSA-N 2-phenoxyacetamide Chemical class NC(=O)COC1=CC=CC=C1 AOPRXJXHLWYPQR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- WBSMIPAMAXNXFS-UHFFFAOYSA-N 5-Nitro-2-(3-phenylpropylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCCC1=CC=CC=C1 WBSMIPAMAXNXFS-UHFFFAOYSA-N 0.000 description 1
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 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
- 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 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- 101710142585 50S ribosomal protein 6, chloroplastic Proteins 0.000 description 1
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-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
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- 102100031901 A-kinase anchor protein 2 Human genes 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100028249 Acetyl-coenzyme A transporter 1 Human genes 0.000 description 1
- 102100021886 Activin receptor type-2A Human genes 0.000 description 1
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 1
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 1
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
- 102100026882 Alpha-synuclein Human genes 0.000 description 1
- 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 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 102100025668 Angiopoietin-related protein 3 Human genes 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 102100025511 Anti-Muellerian hormone type-2 receptor Human genes 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 101100351711 Arabidopsis thaliana PEX14 gene Proteins 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 108010078554 Aromatase Proteins 0.000 description 1
- 102000014654 Aromatase Human genes 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 1
- 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 1
- 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 102100025218 B-cell differentiation antigen CD72 Human genes 0.000 description 1
- 102100035634 B-cell linker protein Human genes 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 1
- 108091012583 BCL2 Proteins 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 102100029945 Beta-galactoside alpha-2,6-sialyltransferase 1 Human genes 0.000 description 1
- 102100021257 Beta-secretase 1 Human genes 0.000 description 1
- 102100021277 Beta-secretase 2 Human genes 0.000 description 1
- 102100038495 Bile acid receptor Human genes 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 101100396232 Bombyx mori EN03 gene Proteins 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100031092 C-C motif chemokine 3 Human genes 0.000 description 1
- 101710155856 C-C motif chemokine 3 Proteins 0.000 description 1
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101710098272 C-X-C motif chemokine 11 Proteins 0.000 description 1
- 101150073986 C3AR1 gene Proteins 0.000 description 1
- 102100021703 C3a anaphylatoxin chemotactic receptor Human genes 0.000 description 1
- 102100034798 CCAAT/enhancer-binding protein beta Human genes 0.000 description 1
- 108010046080 CD27 Ligand Proteins 0.000 description 1
- 108010017987 CD30 Ligand Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 102100027221 CD81 antigen Human genes 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 102100039553 CKLF-like MARVEL transmembrane domain-containing protein 8 Human genes 0.000 description 1
- 102100028226 COUP transcription factor 2 Human genes 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102100024158 Cadherin-10 Human genes 0.000 description 1
- 102100024156 Cadherin-12 Human genes 0.000 description 1
- 102100024154 Cadherin-13 Human genes 0.000 description 1
- 102100022527 Cadherin-18 Human genes 0.000 description 1
- 102100029761 Cadherin-5 Human genes 0.000 description 1
- 102100025331 Cadherin-8 Human genes 0.000 description 1
- 102100025332 Cadherin-9 Human genes 0.000 description 1
- 101100395863 Caenorhabditis elegans hst-2 gene Proteins 0.000 description 1
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 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
- 101100293794 Canis lupus familiaris NME1 gene Proteins 0.000 description 1
- 101710158575 Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase Proteins 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
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 102100032145 Carbohydrate sulfotransferase 10 Human genes 0.000 description 1
- 102100033377 Carbohydrate sulfotransferase 15 Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007275 Carcinoid tumour Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 102100021633 Cathepsin B Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102100035294 Chemokine XC receptor 1 Human genes 0.000 description 1
- 101100004180 Chironomus tentans BR3 gene Proteins 0.000 description 1
- 102000012286 Chitinases Human genes 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 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 1
- 108010038447 Chromogranin A Proteins 0.000 description 1
- 102100031186 Chromogranin-A Human genes 0.000 description 1
- 108010044213 Class 5 Receptor-Like Protein Tyrosine Phosphatases Proteins 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102100031519 Collagen alpha-1(VI) chain Human genes 0.000 description 1
- 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 description 1
- 102100033780 Collagen alpha-3(IV) chain Human genes 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 108090000056 Complement factor B Proteins 0.000 description 1
- 102000003712 Complement factor B Human genes 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 1
- 102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 1
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
- 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- 102100031655 Cytochrome b5 Human genes 0.000 description 1
- 102100026234 Cytokine receptor common subunit gamma Human genes 0.000 description 1
- 102100036952 Cytoplasmic protein NCK2 Human genes 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102100033587 DNA topoisomerase 2-alpha Human genes 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
- 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 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 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 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
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102100028571 Disabled homolog 2-interacting protein Human genes 0.000 description 1
- 102100024364 Disintegrin and metalloproteinase domain-containing protein 8 Human genes 0.000 description 1
- 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 1
- 101100257260 Drosophila melanogaster sob gene Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 1
- 229930193152 Dynemicin Natural products 0.000 description 1
- 102100036254 E3 SUMO-protein ligase PIAS2 Human genes 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 102100033267 Early placenta insulin-like peptide Human genes 0.000 description 1
- AFMYMMXSQGUCBK-UHFFFAOYSA-N Endynamicin A Natural products C1#CC=CC#CC2NC(C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C3)=C3C34OC32C(C)C(C(O)=O)=C(OC)C41 AFMYMMXSQGUCBK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108010055323 EphB4 Receptor Proteins 0.000 description 1
- 102100031983 Ephrin type-B receptor 4 Human genes 0.000 description 1
- 102100033940 Ephrin-A3 Human genes 0.000 description 1
- 102100023721 Ephrin-B2 Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 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 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 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 1
- 241000283073 Equus caballus Species 0.000 description 1
- 101000617479 Escherichia coli (strain K12) PTS system fructose-like EIIA component Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 102100029951 Estrogen receptor beta Human genes 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 101710082714 Exotoxin A Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 102100026693 FAS-associated death domain protein Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 102100035290 Fibroblast growth factor 13 Human genes 0.000 description 1
- 108050002074 Fibroblast growth factor 17 Proteins 0.000 description 1
- 102100035323 Fibroblast growth factor 18 Human genes 0.000 description 1
- 102100024804 Fibroblast growth factor 22 Human genes 0.000 description 1
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102100037854 G1/S-specific cyclin-E2 Human genes 0.000 description 1
- 102000017700 GABRP Human genes 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 102100036519 Gastrin-releasing peptide Human genes 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 102100033417 Glucocorticoid receptor Human genes 0.000 description 1
- 102000058058 Glucose Transporter Type 2 Human genes 0.000 description 1
- 102100033366 Glutathione hydrolase 1 proenzyme Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)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)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 102100020948 Growth hormone receptor Human genes 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 102100040505 HLA class II histocompatibility antigen, DR alpha chain Human genes 0.000 description 1
- 108010067802 HLA-DR alpha-Chains Proteins 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 102100034676 Hepatocyte cell adhesion molecule Human genes 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100038006 High affinity immunoglobulin epsilon receptor subunit alpha Human genes 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 102100021454 Histone deacetylase 4 Human genes 0.000 description 1
- 102100021453 Histone deacetylase 5 Human genes 0.000 description 1
- 102100038719 Histone deacetylase 7 Human genes 0.000 description 1
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 1
- 101000774738 Homo sapiens A-kinase anchor protein 2 Proteins 0.000 description 1
- 101000970954 Homo sapiens Activin receptor type-2A Proteins 0.000 description 1
- 101000824278 Homo sapiens Acyl-[acyl-carrier-protein] hydrolase Proteins 0.000 description 1
- 101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 1
- 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 description 1
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 1
- 101000693085 Homo sapiens Angiopoietin-related protein 3 Proteins 0.000 description 1
- 101000693801 Homo sapiens Anti-Muellerian hormone type-2 receptor Proteins 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 1
- 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 description 1
- 101000934359 Homo sapiens B-cell differentiation antigen CD72 Proteins 0.000 description 1
- 101000803266 Homo sapiens B-cell linker protein Proteins 0.000 description 1
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 1
- 101000863864 Homo sapiens Beta-galactoside alpha-2,6-sialyltransferase 1 Proteins 0.000 description 1
- 101001111439 Homo sapiens Beta-nerve growth factor Proteins 0.000 description 1
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 1
- 101000894883 Homo sapiens Beta-secretase 2 Proteins 0.000 description 1
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101000934394 Homo sapiens C-C chemokine receptor-like 2 Proteins 0.000 description 1
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000945963 Homo sapiens CCAAT/enhancer-binding protein beta Proteins 0.000 description 1
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000888512 Homo sapiens CKLF-like MARVEL transmembrane domain-containing protein 8 Proteins 0.000 description 1
- 101000860860 Homo sapiens COUP transcription factor 2 Proteins 0.000 description 1
- 101000762229 Homo sapiens Cadherin-10 Proteins 0.000 description 1
- 101000762238 Homo sapiens Cadherin-12 Proteins 0.000 description 1
- 101000762243 Homo sapiens Cadherin-13 Proteins 0.000 description 1
- 101000899405 Homo sapiens Cadherin-18 Proteins 0.000 description 1
- 101000899410 Homo sapiens Cadherin-19 Proteins 0.000 description 1
- 101000794587 Homo sapiens Cadherin-5 Proteins 0.000 description 1
- 101000935111 Homo sapiens Cadherin-7 Proteins 0.000 description 1
- 101000935095 Homo sapiens Cadherin-8 Proteins 0.000 description 1
- 101000935098 Homo sapiens Cadherin-9 Proteins 0.000 description 1
- 101000775595 Homo sapiens Carbohydrate sulfotransferase 10 Proteins 0.000 description 1
- 101000898449 Homo sapiens Cathepsin B Proteins 0.000 description 1
- 101000804783 Homo sapiens Chemokine XC receptor 1 Proteins 0.000 description 1
- 101000941581 Homo sapiens Collagen alpha-1(VI) chain Proteins 0.000 description 1
- 101000940068 Homo sapiens Collagen alpha-1(XVIII) chain Proteins 0.000 description 1
- 101000710873 Homo sapiens Collagen alpha-3(IV) chain Proteins 0.000 description 1
- 101000934320 Homo sapiens Cyclin-A2 Proteins 0.000 description 1
- 101000911952 Homo sapiens Cyclin-dependent kinase 7 Proteins 0.000 description 1
- 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 1
- 101000922386 Homo sapiens Cytochrome b5 Proteins 0.000 description 1
- 101001055227 Homo sapiens Cytokine receptor common subunit gamma Proteins 0.000 description 1
- 101001024712 Homo sapiens Cytoplasmic protein NCK2 Proteins 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000915396 Homo sapiens Disabled homolog 2-interacting protein Proteins 0.000 description 1
- 101000832767 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 8 Proteins 0.000 description 1
- 101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 1
- 101001074629 Homo sapiens E3 SUMO-protein ligase PIAS2 Proteins 0.000 description 1
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000998777 Homo sapiens Early placenta insulin-like peptide Proteins 0.000 description 1
- 101000925241 Homo sapiens Ephrin-A3 Proteins 0.000 description 1
- 101001049392 Homo sapiens Ephrin-B2 Proteins 0.000 description 1
- 101001010910 Homo sapiens Estrogen receptor beta Proteins 0.000 description 1
- 101000911074 Homo sapiens FAS-associated death domain protein Proteins 0.000 description 1
- 101000878124 Homo sapiens Fibroblast growth factor 17 Proteins 0.000 description 1
- 101000878128 Homo sapiens Fibroblast growth factor 18 Proteins 0.000 description 1
- 101001051971 Homo sapiens Fibroblast growth factor 22 Proteins 0.000 description 1
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
- 101000738575 Homo sapiens G1/S-specific cyclin-E2 Proteins 0.000 description 1
- 101000822394 Homo sapiens Gamma-aminobutyric acid receptor subunit pi Proteins 0.000 description 1
- 101000926939 Homo sapiens Glucocorticoid receptor Proteins 0.000 description 1
- 101000997558 Homo sapiens Glutathione hydrolase 1 proenzyme Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000872875 Homo sapiens Hepatocyte cell adhesion molecule Proteins 0.000 description 1
- 101000878611 Homo sapiens High affinity immunoglobulin epsilon receptor subunit alpha Proteins 0.000 description 1
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 description 1
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 description 1
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 description 1
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 description 1
- 101001035752 Homo sapiens Hydroxycarboxylic acid receptor 3 Proteins 0.000 description 1
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 1
- 101001076604 Homo sapiens Inhibin alpha chain Proteins 0.000 description 1
- 101001078133 Homo sapiens Integrin alpha-2 Proteins 0.000 description 1
- 101000994378 Homo sapiens Integrin alpha-3 Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 1
- 101001015006 Homo sapiens Integrin beta-4 Proteins 0.000 description 1
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 1
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 1
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 description 1
- 101001002469 Homo sapiens Interferon lambda-2 Proteins 0.000 description 1
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- 101001076418 Homo sapiens Interleukin-1 receptor type 1 Proteins 0.000 description 1
- 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 description 1
- 101001003147 Homo sapiens Interleukin-11 receptor subunit alpha Proteins 0.000 description 1
- 101000998181 Homo sapiens Interleukin-17B Proteins 0.000 description 1
- 101000998178 Homo sapiens Interleukin-17C Proteins 0.000 description 1
- 101000998151 Homo sapiens Interleukin-17F Proteins 0.000 description 1
- 101000961065 Homo sapiens Interleukin-18 receptor 1 Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001055145 Homo sapiens Interleukin-2 receptor subunit beta Proteins 0.000 description 1
- 101001010626 Homo sapiens Interleukin-22 Proteins 0.000 description 1
- 101000998140 Homo sapiens Interleukin-36 alpha Proteins 0.000 description 1
- 101000998126 Homo sapiens Interleukin-36 beta Proteins 0.000 description 1
- 101000998122 Homo sapiens Interleukin-37 Proteins 0.000 description 1
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 1
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 description 1
- 101000605516 Homo sapiens Kallikrein-12 Proteins 0.000 description 1
- 101000605514 Homo sapiens Kallikrein-13 Proteins 0.000 description 1
- 101001091385 Homo sapiens Kallikrein-6 Proteins 0.000 description 1
- 101001091356 Homo sapiens Kallikrein-9 Proteins 0.000 description 1
- 101000998011 Homo sapiens Keratin, type I cytoskeletal 19 Proteins 0.000 description 1
- 101001046960 Homo sapiens Keratin, type II cytoskeletal 1 Proteins 0.000 description 1
- 101001046936 Homo sapiens Keratin, type II cytoskeletal 2 epidermal Proteins 0.000 description 1
- 101001046952 Homo sapiens Keratin, type II cytoskeletal 2 oral Proteins 0.000 description 1
- 101000934753 Homo sapiens Keratin, type II cytoskeletal 75 Proteins 0.000 description 1
- 101000716729 Homo sapiens Kit ligand Proteins 0.000 description 1
- 101001139130 Homo sapiens Krueppel-like factor 5 Proteins 0.000 description 1
- 101001139126 Homo sapiens Krueppel-like factor 6 Proteins 0.000 description 1
- 101001017969 Homo sapiens Leukotriene B4 receptor 2 Proteins 0.000 description 1
- 101000927946 Homo sapiens LisH domain-containing protein ARMC9 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000739159 Homo sapiens Mammaglobin-A Proteins 0.000 description 1
- 101000739168 Homo sapiens Mammaglobin-B Proteins 0.000 description 1
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 1
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 1
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 1
- 101000628535 Homo sapiens Metalloreductase STEAP2 Proteins 0.000 description 1
- 101000615613 Homo sapiens Mineralocorticoid receptor Proteins 0.000 description 1
- 101000976899 Homo sapiens Mitogen-activated protein kinase 15 Proteins 0.000 description 1
- 101001013159 Homo sapiens Myeloid leukemia factor 2 Proteins 0.000 description 1
- 101000961071 Homo sapiens NF-kappa-B inhibitor alpha Proteins 0.000 description 1
- 101000928278 Homo sapiens Natriuretic peptides B Proteins 0.000 description 1
- 101000995164 Homo sapiens Netrin-4 Proteins 0.000 description 1
- 101000979338 Homo sapiens Nuclear factor NF-kappa-B p100 subunit Proteins 0.000 description 1
- 101000978937 Homo sapiens Nuclear receptor subfamily 0 group B member 2 Proteins 0.000 description 1
- 101000633516 Homo sapiens Nuclear receptor subfamily 2 group F member 6 Proteins 0.000 description 1
- 101001109700 Homo sapiens Nuclear receptor subfamily 4 group A member 1 Proteins 0.000 description 1
- 101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 description 1
- 101001109685 Homo sapiens Nuclear receptor subfamily 5 group A member 2 Proteins 0.000 description 1
- 101001109682 Homo sapiens Nuclear receptor subfamily 6 group A member 1 Proteins 0.000 description 1
- 101001098175 Homo sapiens P2X purinoceptor 7 Proteins 0.000 description 1
- 101000613565 Homo sapiens PRKC apoptosis WT1 regulator protein Proteins 0.000 description 1
- 101001095231 Homo sapiens Peptidyl-prolyl cis-trans isomerase D Proteins 0.000 description 1
- 101000595751 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Proteins 0.000 description 1
- 101000633511 Homo sapiens Photoreceptor-specific nuclear receptor Proteins 0.000 description 1
- 101000613343 Homo sapiens Polycomb group RING finger protein 2 Proteins 0.000 description 1
- 101001056707 Homo sapiens Proepiregulin Proteins 0.000 description 1
- 101000610543 Homo sapiens Prokineticin-2 Proteins 0.000 description 1
- 101000945496 Homo sapiens Proliferation marker protein Ki-67 Proteins 0.000 description 1
- 101001117314 Homo sapiens Prostaglandin D2 receptor 2 Proteins 0.000 description 1
- 101000602015 Homo sapiens Protocadherin gamma-B4 Proteins 0.000 description 1
- 101001110313 Homo sapiens Ras-related C3 botulinum toxin substrate 2 Proteins 0.000 description 1
- 101001132698 Homo sapiens Retinoic acid receptor beta Proteins 0.000 description 1
- 101000739195 Homo sapiens Secretoglobin family 1D member 2 Proteins 0.000 description 1
- 101000716809 Homo sapiens Secretogranin-1 Proteins 0.000 description 1
- 101000651890 Homo sapiens Slit homolog 2 protein Proteins 0.000 description 1
- 101000651893 Homo sapiens Slit homolog 3 protein Proteins 0.000 description 1
- 101000689224 Homo sapiens Src-like-adapter 2 Proteins 0.000 description 1
- 101000713602 Homo sapiens T-box transcription factor TBX21 Proteins 0.000 description 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 101000738413 Homo sapiens T-cell surface glycoprotein CD3 gamma chain Proteins 0.000 description 1
- 101000738335 Homo sapiens T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 1
- 101100425948 Homo sapiens TNFRSF13C gene Proteins 0.000 description 1
- 101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 description 1
- 101000633605 Homo sapiens Thrombospondin-2 Proteins 0.000 description 1
- 101000633617 Homo sapiens Thrombospondin-4 Proteins 0.000 description 1
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
- 101000830560 Homo sapiens Toll-interacting protein Proteins 0.000 description 1
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 101000904152 Homo sapiens Transcription factor E2F1 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 1
- 101000795117 Homo sapiens Triggering receptor expressed on myeloid cells 2 Proteins 0.000 description 1
- 101000851892 Homo sapiens Tropomyosin beta chain Proteins 0.000 description 1
- 101000597779 Homo sapiens Tumor necrosis factor ligand superfamily member 18 Proteins 0.000 description 1
- 101000764263 Homo sapiens Tumor necrosis factor ligand superfamily member 4 Proteins 0.000 description 1
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 101000801254 Homo sapiens Tumor necrosis factor receptor superfamily member 16 Proteins 0.000 description 1
- 101000679903 Homo sapiens Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 description 1
- 101000679857 Homo sapiens Tumor necrosis factor receptor superfamily member 3 Proteins 0.000 description 1
- 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000850748 Homo sapiens Tumor necrosis factor receptor type 1-associated DEATH domain protein Proteins 0.000 description 1
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 101001059220 Homo sapiens Zinc finger protein Gfi-1 Proteins 0.000 description 1
- 101000669028 Homo sapiens Zinc phosphodiesterase ELAC protein 2 Proteins 0.000 description 1
- 101000685848 Homo sapiens Zinc transporter ZIP6 Proteins 0.000 description 1
- 101001026578 Hordeum vulgare Ent-kaurenoic acid oxidase 1 Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 102100039356 Hydroxycarboxylic acid receptor 3 Human genes 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102100034980 ICOS ligand Human genes 0.000 description 1
- 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 1
- 108091058536 IL1F9 Proteins 0.000 description 1
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 1
- 206010021263 IgA nephropathy Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100025885 Inhibin alpha chain Human genes 0.000 description 1
- 102100025305 Integrin alpha-2 Human genes 0.000 description 1
- 102100032819 Integrin alpha-3 Human genes 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102100032999 Integrin beta-3 Human genes 0.000 description 1
- 102100033000 Integrin beta-4 Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102100020990 Interferon lambda-1 Human genes 0.000 description 1
- 102100020989 Interferon lambda-2 Human genes 0.000 description 1
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 1
- 102100026016 Interleukin-1 receptor type 1 Human genes 0.000 description 1
- 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 description 1
- 102100020787 Interleukin-11 receptor subunit alpha Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010089995 Interleukin-13 Receptor alpha1 Subunit Proteins 0.000 description 1
- 102000008035 Interleukin-13 Receptor alpha1 Subunit Human genes 0.000 description 1
- 108010085418 Interleukin-13 Receptor alpha2 Subunit Proteins 0.000 description 1
- 102000007482 Interleukin-13 Receptor alpha2 Subunit Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 102100033105 Interleukin-17C Human genes 0.000 description 1
- 102100033454 Interleukin-17F Human genes 0.000 description 1
- 102100039340 Interleukin-18 receptor 1 Human genes 0.000 description 1
- 108050009288 Interleukin-19 Proteins 0.000 description 1
- 108010082786 Interleukin-1alpha Proteins 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 1
- 108010066979 Interleukin-27 Proteins 0.000 description 1
- 102100033474 Interleukin-36 alpha Human genes 0.000 description 1
- 102100033498 Interleukin-36 beta Human genes 0.000 description 1
- 102100033503 Interleukin-36 gamma Human genes 0.000 description 1
- 102100033502 Interleukin-37 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 1
- 102100026244 Interleukin-9 receptor Human genes 0.000 description 1
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 1
- 102100038318 Kallikrein-12 Human genes 0.000 description 1
- 102100038315 Kallikrein-13 Human genes 0.000 description 1
- 102100034866 Kallikrein-6 Human genes 0.000 description 1
- 102100034876 Kallikrein-9 Human genes 0.000 description 1
- 102100022905 Keratin, type II cytoskeletal 1 Human genes 0.000 description 1
- 102100022854 Keratin, type II cytoskeletal 2 epidermal Human genes 0.000 description 1
- 102100022926 Keratin, type II cytoskeletal 2 oral Human genes 0.000 description 1
- 102100025367 Keratin, type II cytoskeletal 75 Human genes 0.000 description 1
- 108010066302 Keratin-19 Proteins 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 102100020680 Krueppel-like factor 5 Human genes 0.000 description 1
- 102100020679 Krueppel-like factor 6 Human genes 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 102100033375 Leukotriene B4 receptor 2 Human genes 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102100036882 LisH domain-containing protein ARMC9 Human genes 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 101710172064 Low-density lipoprotein receptor-related protein Proteins 0.000 description 1
- 102100040705 Low-density lipoprotein receptor-related protein 8 Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 101150053046 MYD88 gene Proteins 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 208000032271 Malignant tumor of penis Diseases 0.000 description 1
- 108010031029 Mammaglobin B Proteins 0.000 description 1
- 102100037273 Mammaglobin-A Human genes 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 229930126263 Maytansine Natural products 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 102100039373 Membrane cofactor protein Human genes 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 1
- 102100026711 Metalloreductase STEAP2 Human genes 0.000 description 1
- 108010092801 Midkine Proteins 0.000 description 1
- 102100021316 Mineralocorticoid receptor Human genes 0.000 description 1
- 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 1
- 101710151803 Mitochondrial intermediate peptidase 2 Proteins 0.000 description 1
- 102100023483 Mitogen-activated protein kinase 15 Human genes 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000934396 Mus musculus C-C chemokine receptor-like 2 Proteins 0.000 description 1
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 241000428199 Mustelinae Species 0.000 description 1
- 102100026784 Myelin proteolipid protein Human genes 0.000 description 1
- 101710094913 Myelin proteolipid protein Proteins 0.000 description 1
- 102100024134 Myeloid differentiation primary response protein MyD88 Human genes 0.000 description 1
- 102100029687 Myeloid leukemia factor 2 Human genes 0.000 description 1
- 102100031789 Myeloid-derived growth factor Human genes 0.000 description 1
- PHSRRHGYXQCRPU-AWEZNQCLSA-N N-(3-oxododecanoyl)-L-homoserine lactone Chemical compound CCCCCCCCCC(=O)CC(=O)N[C@H]1CCOC1=O PHSRRHGYXQCRPU-AWEZNQCLSA-N 0.000 description 1
- 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 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
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 1
- 102100036836 Natriuretic peptides B Human genes 0.000 description 1
- 101710204212 Neocarzinostatin Proteins 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 108010043296 Neurocan Proteins 0.000 description 1
- 102100030466 Neurocan core protein Human genes 0.000 description 1
- 206010052399 Neuroendocrine tumour Diseases 0.000 description 1
- 101710141525 Neurotoxin 3 Proteins 0.000 description 1
- 108090000095 Neurotrophin-6 Proteins 0.000 description 1
- SYNHCENRCUAUNM-UHFFFAOYSA-N Nitrogen mustard N-oxide hydrochloride Chemical compound Cl.ClCC[N+]([O-])(C)CCCl SYNHCENRCUAUNM-UHFFFAOYSA-N 0.000 description 1
- 108010077641 Nogo Proteins Proteins 0.000 description 1
- 102000010410 Nogo Proteins Human genes 0.000 description 1
- 102100023059 Nuclear factor NF-kappa-B p100 subunit Human genes 0.000 description 1
- 102100023172 Nuclear receptor subfamily 0 group B member 2 Human genes 0.000 description 1
- 102100023171 Nuclear receptor subfamily 1 group D member 2 Human genes 0.000 description 1
- 102100038494 Nuclear receptor subfamily 1 group I member 2 Human genes 0.000 description 1
- 102100029528 Nuclear receptor subfamily 2 group F member 6 Human genes 0.000 description 1
- 102100022679 Nuclear receptor subfamily 4 group A member 1 Human genes 0.000 description 1
- 102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 description 1
- 102100022669 Nuclear receptor subfamily 5 group A member 2 Human genes 0.000 description 1
- 102100022670 Nuclear receptor subfamily 6 group A member 1 Human genes 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108010042215 OX40 Ligand Proteins 0.000 description 1
- 241000238413 Octopus Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 229930187135 Olivomycin Natural products 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 102100037602 P2X purinoceptor 7 Human genes 0.000 description 1
- 108091033411 PCA3 Proteins 0.000 description 1
- 102100040853 PRKC apoptosis WT1 regulator protein Human genes 0.000 description 1
- 101150084398 PTAFR gene Proteins 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 241000609499 Palicourea Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 102100037827 Peptidyl-prolyl cis-trans isomerase D Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 1
- 102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 102100029533 Photoreceptor-specific nuclear receptor Human genes 0.000 description 1
- 101100413173 Phytolacca americana PAP2 gene Proteins 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
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 108700023400 Platelet-activating factor receptors Proteins 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 102100030477 Plectin Human genes 0.000 description 1
- 108010054050 Plectin Proteins 0.000 description 1
- 102100040919 Polycomb group RING finger protein 2 Human genes 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- 108010001511 Pregnane X Receptor Proteins 0.000 description 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 1
- 102100025498 Proepiregulin Human genes 0.000 description 1
- 102100040125 Prokineticin-2 Human genes 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 108010002519 Prolactin Receptors Proteins 0.000 description 1
- 102100029000 Prolactin receptor Human genes 0.000 description 1
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 1
- 102100034836 Proliferation marker protein Ki-67 Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102100024218 Prostaglandin D2 receptor 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108010015499 Protein Kinase C-theta Proteins 0.000 description 1
- 102220586173 Protein downstream neighbor of Son_Y22S_mutation Human genes 0.000 description 1
- 102100021566 Protein kinase C theta type Human genes 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 description 1
- 102100027773 Pulmonary surfactant-associated protein A2 Human genes 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 102100022129 Ras-related C3 botulinum toxin substrate 2 Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 102100028508 Receptor-type tyrosine-protein phosphatase zeta Human genes 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
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 102100033909 Retinoic acid receptor beta Human genes 0.000 description 1
- 108091008770 Rev-ErbAß Proteins 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
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 108010005173 SERPIN-B5 Proteins 0.000 description 1
- 108091006299 SLC2A2 Proteins 0.000 description 1
- 108091006570 SLC33A1 Proteins 0.000 description 1
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 240000003946 Saponaria officinalis Species 0.000 description 1
- 229920002305 Schizophyllan Polymers 0.000 description 1
- 102100037279 Secretoglobin family 1D member 2 Human genes 0.000 description 1
- 102100020867 Secretogranin-1 Human genes 0.000 description 1
- 102100030333 Serpin B5 Human genes 0.000 description 1
- 108010089417 Sex Hormone-Binding Globulin Proteins 0.000 description 1
- 102100030758 Sex hormone-binding globulin Human genes 0.000 description 1
- 102100023980 Signal transducer and activator of transcription 6 Human genes 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 102100027339 Slit homolog 3 protein Human genes 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 108010068542 Somatotropin Receptors Proteins 0.000 description 1
- 102100024510 Src-like-adapter 2 Human genes 0.000 description 1
- 108010048349 Steroidogenic Factor 1 Proteins 0.000 description 1
- 102100029856 Steroidogenic factor 1 Human genes 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 102100036840 T-box transcription factor TBX21 Human genes 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- 102100037911 T-cell surface glycoprotein CD3 gamma chain Human genes 0.000 description 1
- 102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 102000004393 TNF receptor-associated factor 2 Human genes 0.000 description 1
- 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 1
- 102000004399 TNF receptor-associated factor 3 Human genes 0.000 description 1
- 108090000922 TNF receptor-associated factor 3 Proteins 0.000 description 1
- 102000003715 TNF receptor-associated factor 4 Human genes 0.000 description 1
- 108090000008 TNF receptor-associated factor 4 Proteins 0.000 description 1
- 102000003718 TNF receptor-associated factor 5 Human genes 0.000 description 1
- 108090000001 TNF receptor-associated factor 5 Proteins 0.000 description 1
- 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
- 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
- 108010000449 TNF-Related Apoptosis-Inducing Ligand Receptors Proteins 0.000 description 1
- 102000002259 TNF-Related Apoptosis-Inducing Ligand Receptors Human genes 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108010039185 Tenecteplase Proteins 0.000 description 1
- CGMTUJFWROPELF-UHFFFAOYSA-N Tenuazonic acid Natural products CCC(C)C1NC(=O)C(=C(C)/O)C1=O CGMTUJFWROPELF-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 102100029529 Thrombospondin-2 Human genes 0.000 description 1
- 102100029219 Thrombospondin-4 Human genes 0.000 description 1
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102100024652 Toll-interacting protein Human genes 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- IWEQQRMGNVVKQW-OQKDUQJOSA-N Toremifene citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 IWEQQRMGNVVKQW-OQKDUQJOSA-N 0.000 description 1
- 102100024026 Transcription factor E2F1 Human genes 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 102100029678 Triggering receptor expressed on myeloid cells 2 Human genes 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
- 102100036471 Tropomyosin beta chain Human genes 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102100035283 Tumor necrosis factor ligand superfamily member 18 Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 description 1
- 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 description 1
- 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 102100033081 Tumor necrosis factor receptor type 1-associated DEATH domain protein Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 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
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 240000001866 Vernicia fordii Species 0.000 description 1
- 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 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 102000013814 Wnt Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 238000012452 Xenomouse strains Methods 0.000 description 1
- 102100029004 Zinc finger protein Gfi-1 Human genes 0.000 description 1
- 102100039877 Zinc phosphodiesterase ELAC protein 2 Human genes 0.000 description 1
- 102100023144 Zinc transporter ZIP6 Human genes 0.000 description 1
- PVNFMCBFDPTNQI-UIBOPQHZSA-N [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] acetate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 3-methylbutanoate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 2-methylpropanoate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] propanoate Chemical compound CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(C)=O)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2.CCC(=O)O[C@H]1CC(=O)N(C)c2cc(C\C(C)=C\C=C\[C@@H](OC)[C@@]3(O)C[C@H](OC(=O)N3)[C@@H](C)C3O[C@@]13C)cc(OC)c2Cl.CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)C(C)C)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2.CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)CC(C)C)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2 PVNFMCBFDPTNQI-UIBOPQHZSA-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
- 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 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 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
- 108010023617 abarelix Proteins 0.000 description 1
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 1
- 229960002184 abarelix Drugs 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- QUHYUSAHBDACNG-UHFFFAOYSA-N acerogenin 3 Natural products C1=CC(O)=CC=C1CCCCC(=O)CCC1=CC=C(O)C=C1 QUHYUSAHBDACNG-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
- 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 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 108700025316 aldesleukin Proteins 0.000 description 1
- 125000003342 alkenyl group Chemical group 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
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- 108010001818 alpha-sarcin Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229940059260 amidate Drugs 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 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 1
- 229960002932 anastrozole Drugs 0.000 description 1
- 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 1
- 229950000242 ancitabine Drugs 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229940045799 anthracyclines and related substance 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
- 230000002280 anti-androgenic 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
- 230000000340 anti-metabolite Effects 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
- 238000011394 anticancer treatment Methods 0.000 description 1
- 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 description 1
- 239000013059 antihormonal agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 229940087620 aromasin Drugs 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 108010044540 auristatin Proteins 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 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 1
- 229950011321 azaserine Drugs 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-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
- 229960000997 bicalutamide Drugs 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 229950006844 bizelesin Drugs 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- 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 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 229960005520 bryostatin Drugs 0.000 description 1
- 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 1
- 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 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 108700002839 cactinomycin Proteins 0.000 description 1
- 229950009908 cactinomycin Drugs 0.000 description 1
- 229940088954 camptosar Drugs 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 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 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 229930188550 carminomycin Natural products 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 101150112018 ced-4 gene Proteins 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 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 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- HJWLJNBZVZDLAQ-HAQNSBGRSA-N chembl2103874 Chemical compound C1C[C@@H](CS(=O)(=O)NC)CC[C@@H]1N(C)C1=NC=NC2=C1C=CN2 HJWLJNBZVZDLAQ-HAQNSBGRSA-N 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 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
- 230000012085 chronic inflammatory response Effects 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 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
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 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
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 108700001680 des-(1-3)- insulin-like growth factor 1 Proteins 0.000 description 1
- URLVCROWVOSNPT-QTTMQESMSA-N desacetyluvaricin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 URLVCROWVOSNPT-QTTMQESMSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229950003913 detorubicin Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 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 1
- 229950002389 diaziquone Drugs 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 238000009300 dissolved air flotation Methods 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
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229950004203 droloxifene Drugs 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
- AFMYMMXSQGUCBK-AKMKHHNQSA-N dynemicin a Chemical compound C1#C\C=C/C#C[C@@H]2NC(C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C3)=C3[C@@]34O[C@]32[C@@H](C)C(C(O)=O)=C(OC)[C@H]41 AFMYMMXSQGUCBK-AKMKHHNQSA-N 0.000 description 1
- 229960002759 eflornithine Drugs 0.000 description 1
- 238000001983 electron spin resonance imaging Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 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
- 229950011487 enocitabine Drugs 0.000 description 1
- 108010028531 enomycin Proteins 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229950002973 epitiostanol Drugs 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 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 1
- 229950002017 esorubicin Drugs 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- 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 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 108010038795 estrogen receptors Proteins 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
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 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 1
- 229960000255 exemestane Drugs 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 229950011548 fadrozole Drugs 0.000 description 1
- 229940043168 fareston Drugs 0.000 description 1
- 229940087476 femara Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 108090000047 fibroblast growth factor 13 Proteins 0.000 description 1
- 102000003684 fibroblast growth factor 13 Human genes 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- 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 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- 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 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 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 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229940044658 gallium nitrate Drugs 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 238000001502 gel electrophoresis Methods 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
- 238000001415 gene therapy Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 229940015872 ibandronate Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 229960003685 imatinib mesylate Drugs 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 1
- 229950008097 improsulfan Drugs 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 229940055742 indium-111 Drugs 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 108090000681 interleukin 20 Proteins 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 108040002014 interleukin-18 receptor activity proteins Proteins 0.000 description 1
- 102000008625 interleukin-18 receptor activity proteins Human genes 0.000 description 1
- 108010074109 interleukin-22 Proteins 0.000 description 1
- 108040006852 interleukin-4 receptor activity proteins Proteins 0.000 description 1
- 108040006859 interleukin-5 receptor activity proteins Proteins 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 108040006862 interleukin-9 receptor activity proteins Proteins 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 229950005692 larotaxel Drugs 0.000 description 1
- SEFGUGYLLVNFIJ-QDRLFVHASA-N larotaxel dihydrate Chemical compound O.O.O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@@]23[C@H]1[C@@]1(CO[C@@H]1C[C@@H]2C3)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 SEFGUGYLLVNFIJ-QDRLFVHASA-N 0.000 description 1
- 229960004942 lenalidomide Drugs 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 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
- 229960004338 leuprorelin Drugs 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 102000004311 liver X receptors Human genes 0.000 description 1
- 108090000865 liver X receptors Proteins 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229960003538 lonidamine Drugs 0.000 description 1
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 description 1
- 108010031117 low density lipoprotein receptor-related protein 8 Proteins 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 229960005375 lutein Drugs 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 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
- 230000002101 lytic effect Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm 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
- 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 1
- 229950008612 mannomustine Drugs 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 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 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- 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 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 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 1
- 206010027191 meningioma Diseases 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- 229960003539 mitoguazone Drugs 0.000 description 1
- MXWHMTNPTTVWDM-NXOFHUPFSA-N mitoguazone Chemical compound NC(N)=N\N=C(/C)\C=N\N=C(N)N MXWHMTNPTTVWDM-NXOFHUPFSA-N 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- 210000001616 monocyte Anatomy 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
- 208000037890 multiple organ injury Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000036473 myasthenia Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 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 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 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 1
- 201000008383 nephritis Diseases 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000016065 neuroendocrine neoplasm Diseases 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- 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 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
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 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 1
- 229950005848 olivomycin Drugs 0.000 description 1
- 229950011093 onapristone Drugs 0.000 description 1
- 229950000846 onartuzumab Drugs 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000004819 osteoinduction Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- QVGXLLKOCUKJST-OUBTZVSYSA-N oxygen-17 atom Chemical compound [17O] QVGXLLKOCUKJST-OUBTZVSYSA-N 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- 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 1
- 229940111202 pepsin Drugs 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 108010076042 phenomycin Proteins 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
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 102000030769 platelet activating factor receptor Human genes 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920001583 poly(oxyethylated polyols) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 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
- 238000012545 processing Methods 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 229940087463 proleukin Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000009163 protein therapy Methods 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
- 150000003212 purines Chemical class 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 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 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 108010051412 reteplase Proteins 0.000 description 1
- 229960002917 reteplase Drugs 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 229940120975 revlimid Drugs 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 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
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 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
- XYSQXZCMOLNHOI-UHFFFAOYSA-N s-[2-[[4-(acetylsulfamoyl)phenyl]carbamoyl]phenyl] 5-pyridin-1-ium-1-ylpentanethioate;bromide Chemical compound [Br-].C1=CC(S(=O)(=O)NC(=O)C)=CC=C1NC(=O)C1=CC=CC=C1SC(=O)CCCC[N+]1=CC=CC=C1 XYSQXZCMOLNHOI-UHFFFAOYSA-N 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 229950006315 spirogermanium Drugs 0.000 description 1
- 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 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- 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 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229950009016 tesetaxel Drugs 0.000 description 1
- MODVSQKJJIBWPZ-VLLPJHQWSA-N tesetaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3CC[C@@]2(C)[C@H]2[C@@H](C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C(=CC=CN=4)F)C[C@]1(O)C3(C)C)O[C@H](O2)CN(C)C)C(=O)C1=CC=CC=C1 MODVSQKJJIBWPZ-VLLPJHQWSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 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 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
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 108010042974 transforming growth factor beta4 Proteins 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 1
- 229950001353 tretamine Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229960001670 trilostane Drugs 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
- 229960000875 trofosfamide Drugs 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
- 229950010147 troxacitabine Drugs 0.000 description 1
- 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 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 229960001055 uracil mustard Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940099039 velcade Drugs 0.000 description 1
- 208000024523 vestibulocochlear nerve neoplasm Diseases 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 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 1
- 229960004528 vincristine Drugs 0.000 description 1
- 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 1
- 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 1
- 239000013603 viral vector Substances 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 229950009268 zinostatin Drugs 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- 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
- C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
-
- 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
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- 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
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- 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
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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
- C12N2800/00—Nucleic acids vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
Landscapes
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
本出願は、2014年3月14日出願の米国特許出願第61/953,629号、及び2015年1月26日出願の米国特許出願第62/107,981号、及び2015年1月27日出願の米国特許出願第62/108,476号の優先権を主張し、これらの内容はその全体が参照として本明細書中に援用される。
本出願は、配列表を含み、この配列表はASCII形式でオンライン提出されており、その全体が本明細書により参照として援用される。本ASCIIコピーは、2015年3月12日に、P5804R1−WO_SL.txtというファイル名で作成されており、ファイルサイズは21,971バイトである。
本発明は、概して、分子生物学及びタンパク質工学の分野に関する。より詳細には、本発明は、細菌から異種ポリペプチドを分泌させるためのシグナルペプチドに関する。本発明はまた、原核生物により産生された組換えポリペプチド及びその使用にも関する。
本明細書中記載または参照される技法及び手順は、概して、当業者に十分に理解されており従来の方法論を用いて一般的に使用されるものであり、例えば、Sambrook et al.,Molecular Cloning:A Laboratory Manual 3rd.edition(2001)Cold Spring Harbor Laboratory Press,Cold Spring Harbor,N.Y. CURRENT PROTOCOLS IN MOLECULAR BIOLOGY(F.M. Ausubel, et al. eds.,(2003));the series METHODS IN ENZYMOLOGY(Academic Press, Inc.):PCR 2:A PRACTICAL APPROACH(M.J. MacPherson,B.D. Hames and G.R. Taylor eds.(1995))、Harlow and Lane,eds.(1988)ANTIBODIES,A LABORATORY MANUAL,and ANIMAL CELL CULTURE(R.I. Freshney,ed.(1987))に記載されている広く利用される方法論である。
「ベクター」という用語は、本明細書中使用される場合、自身に連結された別の核酸を輸送することができる核酸分子を示すものとする。ベクターの種類の1つは「プラスミド」であり、プラスミドは、追加のDNAセグメントを連結することができる環状二本鎖DNAループを示す。ベクターの別の種類は、ファージベクターである。ベクターの別の種類は、ウイルスベクターであり、この場合追加のDNAセグメントは、ウイルスゲノムに連結することができる。ある特定のベクターは、それらが導入された宿主細胞中で自律増殖することができる(例えば、細菌の複製開始点を有する細菌ベクター及びエピソーム哺乳類ベクター)。他のベクター(例えば、非エピソーム哺乳類ベクター)は、宿主細胞への導入に際して、宿主細胞のゲノムに組み込み、それにより宿主ゲノムの複製とともに複製させることができる。さらに、ある特定のベクターは、そのベクターが作動可能に連結された遺伝子の発現を指示することができる。そのようなベクターは、本明細書中、「組換え発現ベクター」(または単に「組換えベクター」)と称する。一般に、組換えDNA技法で利用される発現ベクターは、プラスミドの形をしていることが多い。プラスミドが最も一般的に使用される形のベクターであることから、本明細書では、「プラスミド」及び「ベクター」は、同義で用いてもよいものとする。
(a)アミノ酸残基26〜32(L1)、50〜52(L2)、91〜96(L3)、26〜32(H1)、53〜55(H2)、及び96〜101(H3)で生じる超可変ループ(Chothia and Lesk,J. Mol. Biol. 196:901−917(1987));
(b)アミノ酸残基24〜34(L1)、50〜56(L2)、89〜97(L3)、31〜35b(H1)、50〜65(H2)、及び95〜102(H3)で生じるCDR(Kabat et al.,Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service,National Institutes of Health,Bethesda,MD(1991));
(c)アミノ酸残基27c〜36(L1)、46〜55(L2)、89〜96(L3)、30〜35b(H1)、47〜58(H2)、及び93〜101(H3)で生じる抗原接触部(MacCallum et al. J. Mol. Biol. 262:732−745(1996));及び
(d)HVRアミノ酸残基46〜56(L2)、47〜56(L2)、48〜56(L2)、49〜56(L2)、26〜35(H1)、26〜35b(H1)、49〜65(H2)、93〜102(H3)、及び94〜102(H3)を含む、(a)、(b)、及び/または(c)の組み合わせ。
他に特に記載がない限り、可変ドメイン中のHVR残基及び他の残基(例えば、FR残基)は、本明細書中、Kabat et al.,(上記)に従って番号付けされる。
本明細書中提供するのは、例えば、異種ポリペプチド(例えば、抗体、例えば、全長抗体)の製造方法に適した、シグナルペプチド、及び変異型シグナルペプチドを用いた方法である。シグナルペプチドを特性決定する方法は、当該分野で既知である。1つの図式において、シグナルペプチドは、一般的に3つの異なる領域から構成される:1つまたは2つの正電荷を帯びたアミノ酸残基を含有するN末端領域、H領域と称する(Hドメインとも呼ぶ)ことの多い疎水性コア領域、及びシグナルペプチダーゼにより認識されるC末端領域である。いくつかの実施形態において、H領域は、長さが約10〜16残基である。シグナルペプチドの疎水性は、アイゼンベルグ尺度を用いて計算してもよい。Eisenberg,D. et al,J Mol Biol(1984)179:125−142を参照。簡単に述べると、各アミノ酸に、正規化された統一疎水性値を割り当てる(Eisenberg, et al.上記、表I(126頁)を参照)。シグナルペプチドの各アミノ酸の統一疎水性値(または、例えば、H領域の総合疎水性値を計算するために、H領域の各アミノ酸の統一疎水性値)を合計することで、合計疎水性(総合疎水性とも呼ぶ)を計算する。平均疎水性は、以下の式を用いて計算する:平均疎水性=総合(合計)疎水性/アミノ酸の数。いくつかの実施形態において、全シグナルペプチドの平均疎水性が計算される。いくつかの実施形態において、H領域(Hドメインとも呼ぶ)の平均疎水性が計算される。
異種ポリペプチドの例として、膜貫通分子(例えば、受容体チロシンキナーゼなどの受容体)または増殖因子などのリガンドが挙げられる。異種ポリペプチドの例として、分子、例えばレニンなど;ヒト成長ホルモン及びウシ成長ホルモンをはじめとする成長ホルモン;成長ホルモン放出因子;副甲状腺ホルモン;甲状腺刺激ホルモン;リポタンパク質;アルファ−1−アンチトリプシン;インシュリンA鎖;インシュリンB鎖;プロインシュリン;卵胞刺激ホルモン;カルシトニン;黄体ホルモン;グルカゴン;凝固因子、例えば、第VIIIC因子、第IX因子、組織因子(TF)、及びフォン・ヴィルブランド因子など;抗凝固因子、例えばタンパク質Cなど;心房性ナトリウム利尿因子;肺界面活性物質;プラスミノーゲン活性化因子、例えばウロキナーゼまたはヒト尿または組織型プラスミノーゲン活性化因子(t−PA)など;ボンベシン;トロンビン;造血性成長因子;腫瘍壊死因子−アルファ及び−ベータ;エンケファリナーゼ;RANTES(正常T細胞の活性化で制御され、発現し、分泌される物質);ヒトマクロファージ炎症性タンパク質(MIP−1−アルファ);血清アルブミン、例えばヒト血清アルブミンなど;ミュラー管抑制物質;リラキシンA鎖;リラキシンB鎖;プロリラキシン;マウスゴナドトロピン関連ペプチド;微生物タンパク質、例えばベータ−ラクタマーゼなど;DNA分解酵素;IgE;細胞傷害性Tリンパ球関連抗原(CTLA)、例えばCTLA−4など;インヒビン;アクチビン;血管内皮増殖因子(VEGF);ホルモンまたは増殖因子の受容体;タンパク質AまたはD;リウマチ因子;神経栄養因子、例えば骨由来神経栄養因子(BDNF)など、ニューロトロフィン−3、−4、−5、または−6(NT−3、NT−4、NT−5、またはNT−6)、または神経成長因子、例えばNGF−βなど;血小板由来成長因子(PDGF);線維芽細胞増殖因子、例えばaFGF及びbFGFなど;上皮増殖因子(EGF);トランスフォーミング増殖因子(TGF)、例えばTGF−アルファ、及びTGF−β1、TGF−β2、TGF−β3、TGF−β4、またはTGF−β5をはじめとするTGF−ベータなど;インシュリン様増殖因子−I及び−II(IGF−I及びIGF−II);des(1−3)−IGF−I(脳IGF−I)、インシュリン様増殖因子結合タンパク質;CDタンパク質、例えばCD3、CD4、CD8、CD19、CD20、及びCD40など;エリスロポエチン;骨誘導因子;免疫毒素;骨形成タンパク質(BMP);インターフェロン、例えばインターフェロン−アルファ、−ベータ、及び−ガンマなど;コロニー刺激因子(CSF)、例えば、M−CSF、GM−CSF、及びG−CSFなど;インターロイキン(IL)、例えば、IL−1〜IL−10など;スーパーオキシドジスムターゼ;T細胞受容体;表面膜タンパク質;崩壊加速因子;ウイルス抗原、例えば、AIDS外被の一部分など;輸送タンパク質;ホーミング受容体;アドレシン;調節タンパク質;インテグリン、例えばCD11a、CD11b、CD11c、CD18、ICAM、VLA−4、及びVCAM;腫瘍関連抗原、例えば、HER2、HER3、またはHER4受容体など;及び上記のポリペプチドのいずれかの断片が挙げられる。
抗体またはヘテロ多量体ポリペプチドまたはポリペプチドまたはイムノアドヘシンの標的の例として、以下の一覧が挙げられるが、それらに限定されない:BMPI、BMP2、BMP3B(GDFIO)、BMP4、BMP6、BMP8、CSFI(M−CSF)、CSF2(GM−CSF)、CSF3(G−CSF)、EPO、FGFI(aFGF)、FGF2(bFGF)、FGF3(int−2)、FGF4(HST)、FGF5、FGF6(HST−2)、FGF7(KGF)、FGF9、FGF10、FGF11、FGF12、FGF12B、FGF14、FGF16、FGF17、FGF19、FGF20、FGF21、FGF23、IGF1、IGF2、IFNAI、IFNA2、IFNA4、IFNA5、IFNA6、IFNA7、IFNBI、IFNG、IFNWI、FELI、FELI(EPSELON)、FELI(ZETA)、IL1A、IL1B、IL2、IL3、IL4、IL5、IL6、IL7、IL8、IL9、IL10、IL11、IL12A、IL12B、IL13、IL14、IL15、IL16、IL17、IL17B、IL18、IL19、IL20、IL22、IL23、IL24、IL25、IL26、IL27、IL28A、IL28B、IL29、IL30、PDGFA、PDGFB、TGFA、TGFB1、TGFB2、TGFB3、LTA(TNF−b)、LTB、TNF(TNF−a)、TNFSF4(OX40リガンド)、TNFSF5(CD40リガンド)、TNFSF6(FasL)、TNFSF7(CD27リガンド)、TNFSF8(CD30リガンド)、TNFSF9(4−1BBリガンド)、TNFSFIO(TRAIL)、TNFSF1I(TRANCE)、TNFSF12(AP03L)、TNFSF13(April)、TNFSF13B、TNFSF14(HVEM−L)、TNFSF15(VEGI)、TNFSF18、HGF(VEGFD)、VEGF、VEGFB、VEGFC、ILIR1、IL1R2、IL1RL1、IL1RL2、IL2RA、IL2RB、IL2RG、IL3RA、IL4R、IL5RA、IL6R、IL7R、IL8RA、IL8RB、IL9R、ILIORA、ILIORB、IL11RA、IL12RB1、IL12RB2、IL13RA1、IL13RA2、IL15RA、IL17R、IL18R1、IL20RA、IL21R、IL22R、IL1HY1、IL1RAP、IL1RAPL1、IL1RAPL2、IL1RN、IL6ST、IL18BP、IL18RAP、IL22RA2、AIFI、HGF、LEP(レプチン)、PTN、THPO、CCLI(I−309)、CCL2(MCP−1/MCAF)、CCL3(MIP−la)、CCL4(MIP−lb)、CCL5(RANTES)、CCL7(MCP−3)、CCL8(mcp−2)、CCLH(エオタキシン)、CCL13(MCP−4)、CCL15(MIP−ld)、CCL16(HCC−4)、CCL17(TARC)、CCL18(PARC)、CCL19(MDP−3b)、CCL20(MIP−3a)、CCL21(SLC/エクソダス−2)、CCL22(MDC/STC−I)、CCL23(MPIF−I)、CCL24(MPIF−2/エオタキシン−2)、CCL25(TECK)、CCL26(エオタキシン−3)、CCL27(CTACK/ILC)、CCL28、CXCLI(GROI)、CXCL2(GR02)、CXCL3(GR03)、CXCL5(ENA−78)、CXCL6(GCP−2)、CXCL9(MIG)、CXCL10(IP10)、CXCL11(I−TAC)、CXCL12(SDFI)、CXCL13、CXCL14、CXCL16、PF4(CXCL4)、PPBP(CXCL7)、CX3CL1(SCYDI)、SCYEI、XCLI(リンホタクチン)、XCL2(SCM−lb)、BLRI(MDR15)、CCBP2(D6/JAB61)、CCR1(CKRI/HM145)、CCR2(mcp−IRB/RA)、CCR3(CKR3/CMKBR3)、CCR4、CCR5(CMKBR5/ChemR13)、CCR6(CMKBR6/CKR−L3/STRL22/DRY6)、CCR7(CKR7/EBII)、CCR8(CMKBR8/TERI/CKR−LI)、CCR9(GPR−9−6)、CCRLI(VSHKI)、CCRL2(L−CCR)、XCRI(GPR5/CCXCRI)、CMKLRI、CMKORI(RDCI)、CX3CR1(V28)、CXCR4、GPR2(CCRIO)、GPR31、GPR81(FKSG80)、CXCR3(GPR9/CKR−L2)、CXCR6(TYMSTR/STRL33/Bonzo)、HM74、IL8RA(IL8Ra)、IL8RB(IL8Rb)、LTB4R(GPR16)、TCPIO、CKLFSF2、CKLFSF3、CKLFSF4、CKLFSF5、CKLFSF6、CKLFSF7、CKLFSF8、BDNF、C5R1、CSF3、GRCCIO(CIO)、EPO、FY(DARC)、GDF5、HDFIA、DL8、PRL、RGS3、RGS13、SDF2、SLIT2、TLR2、TLR4、TREMI、TREM2、VHL、ABCFI;ACVRI;ACVRIB;ACVR2;ACVR2B;ACVRLI;AD0RA2A;アグリカン;AGR2;AICDA;AIFI;AIGI;AKAPI;AKAP2;AMH;AMHR2;ANGPTI;ANGPT2;ANGPTL3;ANGPTL4;ANPEP;APC;APOCI;AR;AZGPI(亜鉛−a−糖タンパク質);B7.1;B7.2;BAD;BAFF(BLys);BAGI;BAH;BCL2;BCL6;BDNF;BLNK;BLRI(MDR15);BMPI;BMP2;BMP3B(GDFIO);BMP4;BMP6;BMP8;BMPRIA;BMPRIB;BMPR2;BPAGI(プレクチン);BRCAI;C19orflO(IL27w);C3;C4A;C5;C5R1;CANTI;CASP1;CASP4;CAVI;CCBP2(D6/JAB61);CCLI(1−309);CCLII(エオタキシン);CCL13(MCP−4);CCL15(MlP−ld);CCL16(HCC−4);CCL17(TARC);CCL18(PARC);CCL19(MIP−3b);CCL2(MCP−1);MCAF;CCL20(MIP−3a);CCL21(MTP−2);SLC;エクソダス−2;CCL22(MDC/STC−I);CCL23(MPIF−1);CCL24(MPIF−2/エオタキシン−2);CCL25(TECK);CCL26(エオタキシン−3);CCL27(CTACK/ILC);CCL28;CCL3(MTP−la);CCL4(MDP−lb);CCL5(RANTES);CCL7(MCP−3);CCL8(mcp−2);CCNAI;CCNA2;CCNDI;CCNEI;CCNE2;CCRI(CKRI/HM145);CCR2(mcp−IRB/RA);CCR3(CKR3/CMKBR3);CCR4;CCR5(CMKBR5/ChemR13);CCR6(CMKBR6/CKR−L3/STRL22/DRY6);CCR7(CKR7/EBII);CCR8(CMKBR8/TERI/CKR−LI);CCR9(GPR−9−6);CCRLI(VSHKI);CCRL2(L−CCR);CD164;CD19;CDIC;CD20;CD200;CD22;CD24;CD28;CD3;CD37;CD38;CD3E;CD3G;CD3Z;CD4;CD40;CD40L;CD44;CD45RB;CD52;CD69;CD72;CD74;CD79A;CD79B;CD8;CD80;CD81;CD83;CD86;CDHI(E−カドヘリン);CDH10;CDH12;CDH13;CDH18;CDH19;CDH20;CDH5;CDH7;CDH8;CDH9;CDK2;CDK3;CDK4;CDK5;CDK6;CDK7;CDK9;CDKNIA(p21Wapl/Cipl);CDKNIB(p27Kipl);CDKNIC;CDKN2A(P16INK4a);CDKN2B;CDKN2C;CDKN3;CEBPB;CERI;CHGA;CHGB;キチナーゼ;CHST10;CKLFSF2;CKLFSF3;CKLFSF4;CKLFSF5;CKLFSF6;CKLFSF7;CKLFSF8;CLDN3;CLDN7(クローディン−7);CLN3;CLU(クラスタリン);CMKLRI;CMKORI(RDCI);CNRI;COL18A1;COLIAI;COL4A3;COL6A1;CR2;CRP;CSFI(M−CSF);CSF2(GM−CSF);CSF3(GCSF);CTLA4;CTNNBI(b−カテニン);CTSB(カテプシンB);CX3CL1(SCYDI);CX3CR1(V28);CXCLI(GROI);CXCL10(IP−10);CXCLII(l−TAC/IP−9);CXCL12(SDFI);CXCL13;CXCL14;CXCL16;CXCL2、(GR02);CXCL3(GR03);CXCL5(ENA−78/LIX);CXCL6(GCP−2);CXCL9(MIG);CXCR3(GPR9/CKR−L2);CXCR4;CXCR6(TYMSTR/STRL33/Bonzo);CYB5;CYCI;CYSLTRI;DAB2IP;DES;DKFZp451 J01 18;DNCLI;DPP4;E2F1;ECGFI;EDGI;EFNAI;EFNA3;EFNB2;EGF;EGFR;ELAC2;ENG;EN01;EN02;EN03;EPHB4;EPO;ERBB2(Her−2);EREG;ERK8;ESRI;ESR2;F3(TF);FADD;FasL;FASN;FCERIA;FCER2;FCGR3A;FGF;FGFI(aFGF);FGF10;FGF11;FGF12;FGF12B;FGF13;FGF14;FGF16;FGF17;FGF18;FGF19;FGF2(bFGF);FGF20;FGF21;FGF22;FGF23;FGF3(int−2);FGF4(HST);FGF5;FGF6(HST−2);FGF7(KGF);FGF8;FGF9;FGFR3;FIGF(VEGFD);FELI(EPSILON);FILI(ZETA);FLJ12584;FLJ25530;FLRTI(フィブロネクチン);FLTI;FOS;FOSLI(FRA−I);FY(DARC);GABRP(GABAa);GAGEBI;GAGECI;GALNAC4S−6ST;GAT A3;GDF5;GFI1;GGT1;GM−CSF;GNASI;GNRHI;GPR2(CCRIO);GPR31;GPR44;GPR81(FKSG80);GRCCIO(CIO);GRP;GSN(ゲルゾリン);GSTPI;HAVCR2;HDAC4;HDAC5;HDAC7A;HDAC9;HGF;HIFIA;HDPI;ヒスタミン及びヒスタミン受容体;HLA−A;HLA−DRA;HM74;HMOXI;HUMCYT2A;ICEBERG;ICOSL;ID2;IFN−a;IFNAI;IFNA2;IFNA4;IFNA5;IFNA6;IFNA7;IFNB1;IFNガンマ;DFNWI;IGBPI;IGFI;IGFIR;IGF2;IGFBP2;IGFBP3;IGFBP6;IL−I;IL10;MORA;IL10RB;IL11;IL11RA;IL−12;IL12A;IL12B;IL12RB1;IL12RB2;IL13;IL13RA1;IL13RA2;IL14;IL15;IL15RA;IL16;IL17;IL17B;IL17C;IL17R;IL18;IL18BP;IL18R1;IL18RAP;IL19;IL1A;IL1B;ILIF10;IL1F5;IL1F6;IL1F7;IL1F8;IL1F9;IL1HYI;
IL1Rl;IL1R2;IL1RAP;IL1RAPL1;IL1RAPL2;IL1RL1;IL1RL2、ILIRN;IL2;IL20;IL20RA;IL21R;IL22;IL22R;IL22RA2;IL23;IL24;IL25;IL26;IL27;IL28A;IL28B;IL29;IL2RA;IL2RB;IL2RG;IL3;IL30;IL3RA;IL4;IL4R;IL5;IL5RA;IL6;IL6R;IL6ST(糖タンパク質130);EL7;EL7R;EL8;IL8RA;DL8RB;IL8RB;DL9;DL9R;DLK;INHA;INHBA;INSL3;INSL4;IRAKI;ERAK2;ITGAI;ITGA2;ITGA3;ITGA6(a6インテグリン);ITGAV;ITGB3;ITGB4(b4インテグリン);JAGI;JAKI;JAK3;JUN;K6HF;KAN;KDR;KITLG;KLF5(GC Box BP);KLF6;KLKIO;KLK12;KLK13;KLK14;KLK15;KLK3;KLK4;KLK5;KLK6;KLK9;KRT1;KRT19(ケラチン19);KRT2A;KHTHB6(毛髪特異的H型ケラチン);LAMAS;LEP(レプチン);Lingo−p75;Lingo−Troy;LPS;LTA(TNF−b);LTB;LTB4R(GPR16);LTB4R2;LTBR;MACMARCKS;MAGまたはOmgp;MAP2K7(c−Jun);MDK;MIBI;ミッドカイン;MEF;MIP−2;MKI67;(Ki−67);MMP2;MMP9;MS4A1;MSMB;MT3(メタロチオネクチン−lll);MTSSI;MUCI(ムチン);MYC;MYD88;NCK2;ニューロカン;NFKBI;NFKB2;NGFB(NGF);NGFR;NgR−Lingo;NgR−Nogo66(Nogo);NgR−p75;NgR−Troy;NMEI(NM23A);N0X5;NPPB;NROBI;NR0B2;NRIDI;NR1D2;NR1H2;NR1H3;NR1H4;NR1I2;NR1I3;NR2C1;NR2C2;NR2E1;NR2E3;NR2F1;NR2F2;NR2F6;NR3C1;NR3C2;NR4A1;NR4A2;NR4A3;NR5A1;NR5A2;NR6A1;NRPI;NRP2;NT5E;NTN4;ODZI;OPRDI;P2RX7;PAP;PARTI;PATE;PAWR;PCA3;PCNA;PDGFA;PDGFB;PECAMI;PF4(CXCL4);PGF;PGR;ホスファカン;PIAS2;PIK3CG;PLAU(uPA);PLG;PLXDCI;PPBP(CXCL7);PPID;PRI;PRKCQ;PRKDI;PRL;PROC;PROK2;PSAP;PSCA;PTAFR;PTEN;PTGS2(COX−2);PTN;RAC2(p21 Rac2);RARB;RGSI;RGS13;RGS3;RNFIIO(ZNF144);ROB02;S100A2;SCGB1D2(リポフィリンB);SCGB2A1(マンマグロビン2);SCGB2A2(マンマグロビン1);SCYEI(内皮単球活性化サイトカイン);SDF2;SERPINAI;SERPINA3;SERP1NB5(マスピン);SERPINEI(PAI−I);SERPDMF1;SHBG;SLA2;SLC2A2;SLC33A1;SLC43A1;SLIT2;SPPI;SPRRIB(Sprl);ST6GAL1;STABI;STAT6;STEAP;STEAP2;TB4R2;TBX21;TCPIO;TDGFI;TEK;TGFA;TGFBI;TGFBIII;TGFB2;TGFB3;TGFBI;TGFBRI;TGFBR2;TGFBR3;THIL;THBSI(トロンボスポンジン−1);THBS2;THBS4;THPO;TIE(Tie−1);TMP3;組織因子;TLRIO;TLR2;TLR3;TLR4;TLR5;TLR6;TLR7;TLR8;TLR9;TNF;TNF−a;TNFAEP2(B94);TNFAIP3;TNFRSFIIA;TNFRSFIA;TNFRSFIB;TNFRSF21;TNFRSF5;TNFRSF6(Fas);TNFRSF7;TNFRSF8;TNFRSF9;TNFSFIO(TRAIL);TNFSFI1(TRANCE);TNFSF12(AP03L);TNFSF13(April);TNFSF13B;TNFSF14(HVEM−L);TNFSF15(VEGI);TNFSF18;TNFSF4(OX40リガンド);TNFSF5(CD40リガンド);TNFSF6(FasL);TNFSF7(CD27リガンド);TNFSF8(CD30リガンド);TNFSF9(4−1BBリガンド);TOLLIP;Toll様受容体;TOP2A(トポイソメラーゼEa);TP53;TPMI;TPM2;TRADD;TRAFI;TRAF2;TRAF3;TRAF4;TRAF5;TRAF6;TREMI;TREM2;TRPC6;TSLP;TWEAK;VEGF;VEGFB;VEGFC;バーシカン;VHLC5;VLA−4;XCLI(リンホタクチン);XCL2(SCM−lb);XCRI(GPR5/CCXCRI);YYI;及びZFPM2。
ある特定の実施形態において、本明細書中提供される抗体は、抗体断片である。抗体断片として、Fab、Fab’、Fab’−SH、F(ab’)2、Fv、及びscFv断片、一本腕抗体、ならびに以下に記載される他の断片が挙げられるが、これらに限定されない。ある特定の抗体断片の総説については、Hudson et al.Nat. Med. 9:129−134(2003)を参照。scFv断片の総説については、例えば、Pluckthun,in The Pharmacology of Monoclonal Antibodies,vol. 113,Rosenburg and Moore eds.,(Springer−Verlag、New York),pp.269−315(1994)を参照;同じく、WO93/16185;ならびに米国特許第5,571,894号及び同第5,587,458号を参照。サルベージ受容体結合エピトープ残基を含みin vivo半減期の長くなったFab及びF(ab’)2断片の考察については、米国特許第5,869,046号を参照。
ある特定の実施形態において、本明細書中提供される抗体は、キメラ抗体である。ある特定のキメラ抗体が、例えば、米国特許第4,816,567号;及びMorrison et al.,Proc. Natl. Acad. Sci. USA,81:6851−6855(1984))に記載されている。1つの例において、キメラ抗体は、非ヒト可変領域(例えば、マウス、ラット、ハムスター、ウサギ、またはサルなどの非ヒト霊長類に由来する可変領域)及びヒト定常領域を含む。さらなる例において、キメラ抗体は、親抗体のものと異なるクラスまたはサブクラスに変更された「クラススイッチ」抗体である。キメラ抗体には、キメラ抗体の抗原結合断片も含まれる。
ある特定の実施形態において、本明細書中提供される抗体は、ヒト抗体である。ヒト抗体は、当該分野で既知の様々な技法を用いて製造することができる。ヒト抗体については、van Dijk and van de Winkel,Curr. Opin. Pharmacol. 5:368−74(2001)及びLonberg,Curr. Opin. Immunol. 20:450−459(2008)に総合的な記載がある。
本発明の抗体は、所望の1種の活性または複数の活性を持つ抗体についてコンビナトリアルライブラリーをスクリーニングすることにより、単離されてもよい。例えば、ファージディスプレイライブラリーを作製し、所望の結合特性を保有する抗体についてそのライブラリーをスクリーニングする様々な方法が、当該分野で既知である。そうした方法は、例えば、Hoogenboom et al. in Methods in Molecular Biology 178:1−37(O’Brien et al., ed.,Human Press,Totowa,NJ,2001)に総説が記載されており、さらに、例えば、McCafferty et al.,Nature 348:552−554;Clackson et al.,Nature 352:624−628(1991);Marks et al.,J. Mol. Biol. 222:581−597(1992);Marks and Bradbury,in Methods in Molecular Biology 248:161−175(Lo, ed.,Human Press,Totowa,NJ,2003);Sidhu et al.,J. Mol. Biol. 338(2):299−310(2004);Lee et al.,J. Mol. Biol. 340(5):1073−1093(2004);Fellouse, Proc. Natl. Acad. Sci. USA 101(34):12467−12472(2004);及びLee et al.,J. Immunol. Methods 284(1−2):119−132(2004)に記載されている。
ある特定の実施形態において、本明細書中提供される抗体は、多重特異性抗体、例えば二重特異性抗体である。多重特異性抗体とは、少なくとも2つの異なる部位に対して結合特異性を有するモノクローナル抗体である。ある特定の実施形態において、結合特異性の1つは、c−metに対するものであり、その他は任意の他の抗原に対するものである。ある特定の実施形態において、二重特異性抗体は、c−metの2つの異なるエピトープに結合してもよい。二重特異性抗体はまた、c−metを発現する細胞に細胞障害性剤を局在させるのにも使用することができる。二重特異性抗体は、全長抗体または抗体断片として調製することができる。
ある特定の実施形態において、本明細書中提供される抗体のアミノ酸配列変異体も企図されている。例えば、抗体の結合親和性及び/または他の生物学的性質を改善することが望ましいかもしれない。抗体のアミノ酸配列変異体は、抗体をコードするヌクレオチド配列に適切な修飾を導入することにより、またはペプチド合成により、製造されてもよい。そのような修飾として、例えば、抗体のアミノ酸配列から残基を削除、及び/または抗体のアミノ酸配列に残基を挿入、及び/または抗体のアミノ酸配列内で残基を置換することが挙げられる。削除、挿入、及び置換の任意の組み合わせを行って、最終構築物に到達することができるが、ただし、最終構築物は、所望の特性、例えば、抗原結合性を保持するものである。
多重特異性抗体及び/または一本腕抗体及び/またはイムノアドヘシンを製造する方法としてノブと穴を利用することは、当該分野で既知である。米国特許第5,731,168号(1998年3月4日付与、Genentechに対して譲渡)、PCT公開公報第WO2009089004号(2009年7月16日公開、Amgenに対して譲渡)、及び米国特許出願公開第20090182127号(2009年7月16日公開、Novo Nordisk A/Sに対して譲渡)を参照。Marvin and Zhu,Acta Pharmacologica Sincia(2005)26(6):649−658及びKontermann(2005)Acta Pharacol. Sin., 26:1−9も参照。簡単な説明を、本明細書に提示する。
aアミノ酸分子量から水分子量を引いたもの。Handbook of Chemistry and Physics,43rd ed. Cleveland,Chemical Rubber Publishing Co.,1961より値を引用。
bA.A. Zamyatnin, Prog. Biophys. Mol. Biol. 24:107−123,1972より値を引用。
cC. Chothia,J. Mol. Biol. 105:1−14,1975より値を引用。到達可能表面積は、この引用文献の図6〜20で定義される。
異種ポリペプチド(例えば、抗体)の組換え産生のため、異種ポリペプチドをコードする核酸を単離して、さらなるクローン化(DNAの増幅)用または発現用に反復可能ベクターに挿入する。ポリペプチド(例えば、抗体)をコードするDNAは、従来手順を用いて(例えば、抗体の重鎖及び軽鎖をコードする遺伝子と特異的に結合することができるオリゴヌクレオチドプローブを用いることにより)、容易に単離及び配列決定される。多くのベクターを利用することができる。ベクターの選択は、使用される宿主細胞に一部依存する。一般に、好適な宿主細胞は、原核生物起原いずれかのものである。IgG、IgM、IgA、IgD、及びIgE定常領域をはじめとする任意のアイソタイプの定常領域を、この目的で使用することができ、そのような定常領域は、任意のヒトまたは動物種から得ることができることが理解されるだろう。
i.ベクター構築
本発明のポリペプチド(例えば、抗体)のポリペプチド成分をコードするポリヌクレオチド配列は、標準的な組換え技法を用いて得ることができる。所望のポリヌクレオチド配列は、ハイブリドーマ細胞などの抗体産生細胞から単離して配列決定することができる。あるいは、ポリヌクレオチドは、ヌクレオチド合成機またはPCR技法を用いて合成することができる。いったん得られたら、ポリペプチドをコードする配列を、原核生物宿主で異種ポリヌクレオチドを複製及び発現することができる組換えベクターに挿入する。数多くのベクターが利用可能でありまた当該分野で既知であり、本発明の目的に使用することができる。適切なベクターの選択は、ベクターに挿入する予定の核酸のサイズ及びそのベクターで形質転換する予定の特定の宿主細胞に主に依存する。各ベクターは、その機能(異種ポリヌクレオチドの増幅または発現、あるいは両方)及びそのベクターが滞在する特定の宿主細胞との適合性に応じて、様々な成分を含有する。ベクター成分として、一般に以下が挙げられるが、それらに限定されない:複製開始点、選択マーカー遺伝子、プロモーター、リボソーム結合部位(RBS)、シグナル配列、異種核酸挿入物、及び転写終結配列。
宿主細胞を、上記の発現ベクターで形質転換して、プロモーターを誘導し、形質転換体を選択し、または所望の配列をコードする遺伝子を増幅するのに適切なように修飾された通常の栄養培地で培養する。
当該分野で既知の標準的なタンパク質精製方法を採用することができる。以下の手順は、適切な精製手順の例である:免疫親和性またはイオン交換カラムでの分画、エタノール沈殿、逆相HPLC、シリカでのまたはDEAEなどの陽イオン交換樹脂でのクロマトグラフィー、クロマトフォーカシング、SDS−PAGE、硫酸アンモニウム沈殿、及び、例えば、Sephadex G−75を用いるゲル濾過。
異種ポリペプチドは、例えば、そのポリペプチドが認識する特定のポリペプチドを精製、検出、及び標的とするのに使用することができ、そのような用途として、in vitro及びin vivo両方での診断方法及び治療方法が挙げられる。
本発明の別の実施形態において、上記の障害の治療に有用な物質を含有する製品を提供する。製品は、容器、及び容器上のまたは容器に付随するラベルまたは添付文書を含む。適切な容器として、例えば、瓶、バイアル、シリンジなどが挙げられる。容器は、ガラスまたはプラスチックなど様々な材料から形成されていてよい。容器は、症状を治療するのに有効な組成物を収容し、滅菌の出し入れ口を有していてもよい(例えば、容器は、皮下注射針で穴をあけることができる栓を有する、静脈内注射液の袋またはバイアルであってもよい)。組成物の活性成分の少なくとも1種は、本発明の抗体である。ラベルまたは添付文書は、その組成物が、特定の症状、例えば癌などの治療に使用されることを示す。そのうえ、製品は、(a)抗体を含む組成物が入った第一容器;及び(b)さらなる細胞障害性剤を含む組成物が入った第二容器を含んでもよい。本発明のこの実施形態の製品は、さらに、第一及び第二の抗体組成物が、癌治療に使用可能であることを示す添付文書を含んでもよい。あるいは、またはそれに加えて、製品は、薬学上許容される緩衝液、例えば注射用静菌水(BWFI)、リン酸緩衝生理食塩水、リンガー溶液、及びブドウ糖液を含む第二(または第三)容器をさらに含んでもよい。製品は、商業及び使用者の立場から望ましい他の材料をさらに含んでもよく、そのような材料として、他の緩衝液、希釈剤、フィルター、針、及びシリンジが挙げられる。
株及びプラスミド。この試験で使用した株及びプラスミドを表1に列挙する。重鎖のみの発現ベクターを構築するため、全長抗体発現ベクターを、SpeI及びNsiI(New England Biolabs)で消化した。シグナルペプチド配列及び重鎖配列を含有して得られる断片を、pBR322由来クローニングベクターのSpeI及びNsiI部位にクローン導入した。pBR322由来クローニングベクターは、切断型軽鎖断片(122−237)、重鎖配列と融合したphoAプロモーター、及びラムダt0転写ターミネーターを含むものであった。ακLc抗体をプローブとして用いるウエスタンブロット分析により、この重鎖のみのベクターで軽鎖は発現しなかったことを確認した。翻訳強度測定用のPhoAレポータープラスミドを構築するため、目的のシグナルペプチド変異体を、通常PCRまたはスプライシングオーバーラップ伸長(SOE)PCR法を介してphoA遺伝子と融合させた。得られた断片を、pPhoA51のSpeI及びNotI(New England Biolabs)部位にクローン導入した[1]。シグナルペプチド配列の部位特異的変異を、QuickChange部位特異的変異誘発キット(Stratagene)により導入した。
重鎖N末端のEdman配列決定。震盪フラスコ培養物から採取した終点試料を、OD550を1として正規化し、16,000×gで3分間遠心することにより採取した。ペレットを、0.2MのDTT含有トリシン緩衝液200μLに再懸濁させ、95℃で5分間加熱した。タンパク質を、8%または10%ビス−トリスSDS−PAGEゲル(Life Technologies)での電気泳動により分離させた。空のpBR322ベクターを抱える64B4由来のOD550が1または4の細胞溶解液もまた、対照として添加した。電気泳動後、タンパク質を、CAPS緩衝液での湿式トランスファー(Biorad)によりPVDF膜に移した。膜上の約49kDaの重鎖バンドを切り出し、Applied Biosystems Procise配列決定装置モデル494HTを用いて、Edman配列決定により分析した。成熟重鎖対前駆体の比を、ピーク強度に基づいて見積もった。半定量化のため、各アミノ酸のピコモル値を、配列分析プログラムSEQXを用いて、未補正のフェニルチオヒダントインアミノ酸標準に対して計算した(Henzel et al.,Journal of Chromatography,1987)。10回のサイクルの平均を用いて、平均反応収率プロットを作成し、直線回帰を計算して、主要及び少数配列の初収量を、プロットした直線のy接線と定義した。重鎖プロセシング効率を、分泌された重鎖のパーセンテージ(成熟重鎖の初収量/(前駆体の初収量+成熟重鎖の初収量))として計算した。
E.coliでの抗体(例えば全長抗体)産生は、抗体重鎖及び軽鎖が細胞質からペリプラズムへ分泌されることにより達成され得る[2]。分泌には、重鎖及び軽鎖のN末端に融合したE.coliシグナルペプチドが介在する。ペリプラズムの酸化環境及び酵素は、重鎖及び軽鎖が抗体へと構築されるのを促進する。異種タンパク質(例えば、抗体)の高レベル産生手段としてペリプラズム分泌を利用することは、頻繁に遭遇する問題が複数あるために、制限される可能性がある。第一に、目的のタンパク質(例えば、抗体)の分泌効率が低い可能性がある。第二に、多くの場合、前駆体が成熟タンパク質になるプロセシングが不十分である。第三に、過剰発現した異種タンパク質は、不適切に折り畳まれるか、凝集して不溶性封入体になるか、またはE.coliプロテアーゼによりタンパク質分解を受けることが多い。第四に、抗体は、2つの異なるポリペプチド、重鎖(HC)及び軽鎖(LC)からなる複雑な多量体タンパク質であり、これらポリペプチドがペリプラズムに搬出されて、適切に折り畳まれて、適切なジスルフィド結合を形成しなければならない。このタンパク質の折り畳み及び分泌の複雑さが、E.coliでの抗体製造に困難さを加えている。
下線=アミノ酸配列中の変異
合計疎水性(sum hydro)は、Eisenbergらにより開発された正規化共通尺度[20]に基づいて計算。
平均疎水性=シグナル配列の合計疎水性をアミノ酸残基の個数で割ったもの
合計疎水性(H)=H領域の合計疎水性
平均疎水性(H)=H領域の平均疎水性
太字=BssHII、MluI、またはXbaI制限部位
下線=アミノ酸配列を変更するためになされた変異
*推定成熟/前駆体比は、ピーク強度の概算に基づく。
**分泌HC%は、材料及び方法の節で記載したとおり、成熟重鎖及び前駆体の初収量の半定量化により求める。
*分泌HC%は、材料及び方法の節で記載したとおり、成熟重鎖及び前駆体の初収量の半定量化により求める。
*分泌HC%は、材料及び方法の節で記載したとおり、成熟重鎖及び前駆体の初収量の半定量化により求める。
1. Simmons, L.C. and D.G. Yansura,Nat Biotechnol,1996.14(5):p.629−34.
2. Simmons, L.C., et al.,J Immunol Methods,2002.263(1−2):p.133−47.
3. US 8361744
4. Quan,S., et al.,Methods Mol Biol,2013.966:p.359−66.
5. Oliver, D.B. and J. Beckwith,Cell,1982.30(1):p.311−9.
6. Auclair, S.M., M.K. Bhanu, and D.A. Kendall,Protein Sci,2012.21(1):p.13−25.
7. Josefsson, L.G. and L.L. Randall,Cell,1981.25(1):p.151−7.
8. Izard JW, K.D.,Mol Microbiol,1994.13(5):p.765−73.
Claims (81)
- E.coli宿主細胞からの抗体重鎖及び/または抗体軽鎖の分泌の増加方法であって、(1)抗体重鎖をコードするポリヌクレオチドと作動可能に連結された第一シグナルペプチドをコードする第一ポリヌクレオチドであって、前記シグナルペプチドの平均疎水性は約0.5超である、前記第一ポリヌクレオチド;及び/または(2)抗体軽鎖をコードするポリヌクレオチドと作動可能に連結された第二シグナルペプチドをコードする第二ポリヌクレオチドであって、前記第二シグナルペプチドの平均疎水性は約0.5超である前記第二ポリヌクレオチド、を含むポリヌクレオチドを含み、そうすることにより、宿主細胞での抗体の発現に際して、前記重鎖及び軽鎖が折り畳まれ構築されて、生物学的に活性な抗体を形成する、E.coli宿主細胞を培養することを含む、前記方法。
- 前記第一シグナルペプチドの前記疎水性は、約0.6超である、請求項1に記載の方法。
- 前記第二シグナルペプチドの前記疎水性は、約0.6超である、請求項1または2に記載の方法。
- 前記第一及び/または第二シグナルペプチドは、変異型共翻訳シグナルペプチドである、請求項1から3のいずれか1項に記載の方法。
- 前記第一及び/または第二シグナルペプチドは、変異型DsbAシグナルペプチドである、請求項1から4のいずれか1項に記載の方法。
- 前記変異型DsbAシグナルペプチドは、残基L11に変異を有し、前記変異型DsbAシグナルペプチドは、配列番号3の野生型DsbAシグナルペプチドよりも高い平均疎水性を有する、請求項5に記載の方法。
- 前記変異は、L11IまたはS18Yである、請求項6に記載の方法。
- 前記変異型DsbAシグナルペプチドは、配列番号13または15の配列を含む、請求項5に記載の方法。
- 前記シグナルペプチドは、Sfmcシグナルペプチドである、請求項1から4のいずれか1項に記載の方法。
- 前記第一及び/または第二シグナルペプチドのTIR強度は、約1、約2、約3、約4、約5、約6、約7、または約8である、請求項1から9のいずれか1項に記載の方法。
- 前記第一シグナルペプチドの前記TIR強度は、約5であり、かつ前記第二シグナル配列の前記TIR強度は、約8である、請求項10に記載の方法。
- 前記宿主細胞中の前記ポリヌクレオチドは、さらに、プロモーターを含む、請求項1から11のいずれか1項に記載の方法。
- 前記プロモーターは、phoA、tac、lpp、lac−lpp、lac、ara、及びT7プロモーターからなる群より選択される原核生物プロモーターである、請求項12に記載の方法。
- 前記E.coli宿主細胞は、内因性プロテアーゼ活性が欠損した株のものである、請求項1から14のいずれか1項に記載の方法。
- 前記E.coliの遺伝子型は、degP遺伝子及びprc遺伝子を欠いており、かつ突然変異spr遺伝子を抱えている、請求項14に記載の方法。
- 前記宿主細胞は、さらに、DsbA、DsbC、DsbG、及びFkpAからなる群より選択される少なくとも1種の原核生物ポリペプチドをコードするポリヌクレオチドを含む、請求項1から15のいずれか1項に記載の方法。
- 前記ポリヌクレオチドは、DsbA及びDsbCの両方をコードする、請求項16に記載の方法。
- 宿主細胞培養物から抗体を回収することをさらに含む、請求項1から17のいずれか1項に記載の方法。
- 前記抗体は、宿主細胞培養培地から回収される、請求項18に記載の方法。
- 前記回収した抗体を、薬学上許容される担体、賦形剤、または担体と組み合わせて、前記抗体を含む医薬製剤を調剤することを含む、請求項18または19に記載の方法。
- 形成される免疫グロブリンポリペプチド複合体のうち少なくとも50%は、前記抗体である、請求項19に記載の方法。
- 形成される免疫グロブリンポリペプチド複合体のうち少なくとも70%は、前記抗体である、請求項19に記載の方法。
- 前記抗体は、モノクローナル抗体である、請求項1から22のいずれか1項に記載の方法。
- 前記抗体は、キメラ抗体、親和性成熟抗体、二重特異性抗体、ヒト化抗体、またはヒト抗体である、請求項23に記載の方法。
- 前記抗体は、二重特異性抗体である、請求項23に記載の方法。
- 平均疎水性が0.5超であるH領域を含む、変異型DsbAシグナルペプチド。
- 配列番号3のDsbAシグナルペプチドよりも高い平均疎水性を有する、残基S11に変異を含む変異型DsbAシグナルペプチド。
- 前記変異は、L11I及び/またはS18Yである、請求項27に記載の変異型DsbAシグナルペプチド。
- 配列番号1のSTIIシグナルペプチドよりも高い平均疎水性を有する、残基S11に変異を含む変異型STIIシグナルペプチド。
- 前記変異は、S11A、S11I、またはS11Lである、請求項29に記載の変異型STIIシグナルペプチド。
- 配列番号8、11、13、15、31、または33の配列からなる、本質的にその配列からなる、またはその配列を含む、変異型シグナルペプチド。
- 異種タンパク質と融合した、請求項26から30のいずれか1項に記載の変異型シグナルペプチド。
- 前記異種ポリペプチドは、抗体重鎖である、請求項32に記載の変異型シグナルペプチド。
- 前記異種ポリペプチドは、抗体軽鎖である、請求項32に記載の変異型シグナルペプチド。
- 前記異種ポリペプチドは、抗体軽鎖及び重鎖である、請求項32に記載の変異型シグナルペプチド。
- 前記異種ポリペプチドは、多量体ポリペプチドである、請求項32に記載の変異型シグナルペプチド。
- 前記異種ポリペプチドは、イムノアドヘシンである、請求項32に記載の変異型シグナルペプチド。
- 請求項26から30のいずれか1項に記載の変異型シグナルペプチドをコードするポリヌクレオチド配列。
- 異種ポリペプチドをコードするポリヌクレオチドと作動可能に連結した請求項38に記載のポリヌクレオチド配列であって、それにより、宿主細胞中での前記異種ポリペプチドの発現に際して、前記異種ポリペプチドは折り畳まれ構築されて、生物学的に活性な異種ポリペプチドを形成する、ポリヌクレオチド配列。
- 前記宿主細胞は、原核生物宿主細胞である、請求項39に記載のポリヌクレオチド配列。
- 前記宿主細胞は、E.coliである、請求項40に記載のポリヌクレオチド配列。
- 抗体をコードするポリヌクレオチドであって、前記ポリヌクレオチドは、(1)抗体重鎖をコードするポリヌクレオチドと作動可能に連結した第一シグナルペプチドをコードするポリヌクレオチド、及び(2)抗体軽鎖をコードするポリヌクレオチドと作動可能に連結した第二シグナルペプチドをコードするポリヌクレオチドを含み、それにより、宿主細胞中での前記抗体発現の際に、前記重鎖及び軽鎖が折り畳まれ構築されて、生物学的に活性な抗体を形成し、前記第一シグナルペプチドは請求項26から30のいずれか1項に記載の変異型シグナルペプチドであるか、または前記第一シグナルペプチドは、配列番号8、11、13、15、31、33、または42の配列からなる、本質的にその配列からなる、またはその配列を含む、前記ポリヌクレオチド。
- 前記第一シグナルペプチドは、請求項26から30のいずれか1項に記載の変異型シグナルペプチドである、請求項42に記載のポリヌクレオチド。
- 前記第一シグナルペプチドは、配列番号8、11、13、15、31、33、または42の配列からなる、本質的にその配列からなる、またはその配列を含む、請求項42に記載のポリヌクレオチド。
- 前記第二シグナルペプチドは、シグナルペプチドである、請求項42から44のいずれか1項に記載のポリヌクレオチド。
- 前記第二シグナルペプチドは、請求項26から30のいずれか1項に記載の変異型シグナルペプチドであるか、あるいは前記第二シグナルペプチドは、配列番号8、11、13、15、31、33、または42の配列からなる、本質的にその配列からなる、またはその配列を含む、請求項42から44のいずれか1項に記載のポリヌクレオチド。
- 前記第二シグナルペプチドは、請求項26から30のいずれか1項に記載の変異型シグナルペプチドである、請求項42から44のいずれか1項に記載のポリヌクレオチド。
- 前記第二シグナルペプチドは、配列番号8、11、13、15、31、33、または42の配列からなる、本質的にその配列からなる、またはその配列を含む、請求項42から44のいずれか1項に記載のポリヌクレオチド。
- 抗体をコードする前記ポリヌクレオチドは、さらに、(3)Fcポリペプチドをコードするポリヌクレオチドと作動可能に連結した第三シグナルペプチドをコードするポリペプチドを含む、請求項42から48のいずれか1項に記載のポリヌクレオチド。
- 前記第三シグナルペプチドは、請求項26から30のいずれか1項に記載の変異型シグナルペプチドであるか、あるいは前記第三シグナルペプチドは、配列番号8、11、13、15、31、33、または42の配列からなる、本質的にその配列からなる、またはその配列を含む、請求項49に記載のポリヌクレオチド。
- 前記異種ポリペプチドと作動可能に連結したプロモーターをさらに含む、請求項39から50のいずれか1項に記載のポリヌクレオチド。
- 前記プロモーターは、phoA、tac、lpp、lac−lpp、lac、ara、trp、及びT7プロモーターからなる群より選択される原核生物プロモーターである、請求項51に記載のポリヌクレオチド。
- 前記プロモーターは、phoAプロモーターである、請求項52に記載のポリヌクレオチド。
- (a)第一プロモーターであって、軽鎖と作動可能に連結している前記第一プロモーター、及び(b)第二プロモーターであって、重鎖と作動可能に連結している前記第二プロモーター、をさらに含む、請求項39から53のいずれか1項に記載のポリヌクレオチド。
- 前記第一プロモーター及び第二プロモーターは、両方ともphoAプロモーターである、請求項54に記載のポリヌクレオチド。
- (c)第三プロモーターであって、Fcポリペプチドと作動可能に連結している前記第三プロモーター、をさらに含む、請求項54に記載のポリヌクレオチド。
- 前記プロモーターは、phoAプロモーターである、請求項56に記載のポリヌクレオチド。
- 前記異種ポリペプチドは、プロテアーゼ、イムノアドヘシン、受容体の細胞外ドメイン、ヘテロ多量体タンパク質、または抗体である、請求項39から41のいずれか1項に記載のポリヌクレオチド。
- 前記抗体は、モノクローナル抗体である、請求項42から57のいずれか1項に記載のポリヌクレオチド。
- 前記抗体は、キメラ抗体、二重特異性抗体、ヒト化抗体、抗体断片、またはヒト抗体である、請求項59に記載のポリヌクレオチド。
- 前記抗体断片は、一本腕抗体である、請求項59に記載のポリヌクレオチド。
- 前記抗体は、二重特異性抗体である、請求項59に記載のポリヌクレオチド。
- 請求項39から62のいずれか1項に記載のポリヌクレオチドを含むベクター。
- 発現ベクターである、請求項63に記載のベクター。
- 請求項39から62のいずれか1項に記載のポリヌクレオチドを含む組成物。
- 請求項64に記載のベクターを含む、宿主細胞。
- 原核細胞である、請求項66に記載の宿主細胞。
- 前記原核細胞は、E.coliである、請求項67に記載の宿主細胞。
- 前記E.coliは、内因性プロテアーゼ活性が欠損した株のものである、請求項68に記載の宿主細胞。
- 前記E.coliの遺伝子型は、degP遺伝子及びprc遺伝子を欠いており、かつ突然変異spr遺伝子を抱えている、請求項68または69に記載の宿主細胞。
- 原核生物シャペロンタンパク質をコードするポリヌクレオチドをさらに含む、請求項66から70のいずれか1項に記載の宿主細胞。
- 前記原核生物シャペロンタンパク質は、DsbA及び/またはDsbCである、請求項71に記載の宿主細胞。
- 原核生物シャペロンタンパク質を過剰発現する、請求項71または72に記載の宿主細胞。
- 異種ポリペプチド(抗体重鎖及び/または軽鎖など)の作成方法であって、請求項66から73のいずれか1項に記載の宿主細胞を、核酸が発現されるように培養することを含み、それにより、宿主細胞中での前記ポリヌクレオチドの発現の際に、前記異種ポリペプチドが折り畳まれて生物学的に活性な異種ポリペプチドを形成する、前記方法。
- 宿主細胞培養物から前記異種ポリペプチドを回収することをさらに含む、請求項74に記載の方法。
- 前記異種ポリペプチドは、宿主細胞培養培地から回収される、請求項75に記載の方法。
- 前記回収した異種ポリペプチドを、薬学上許容される担体、賦形剤、または担体と組み合わせて、前記異種ポリペプチドを含む医薬製剤を調剤することをさらに含む、請求項74または75に記載の方法。
- 細胞からの異種ポリペプチド(抗体重鎖及び/または軽鎖など)の分泌方法であって、請求項66から73のいずれか1項に記載の宿主細胞を、核酸が発現され、かつ前記異種ポリペプチドが分泌されるように培養することを含む、前記方法。
- 細胞からの異種ポリペプチド(抗体重鎖及び/または軽鎖など)の移行方法であって、請求項66から73のいずれか1項に記載の宿主細胞を、核酸が発現され、かつ前記異種ポリペプチドが移行されるように培養することを含む、前記方法。
- 請求項74から79のいずれか1項に記載の方法により得られる異種ポリペプチド。
- 抗体である、請求項80に記載のポリペプチド。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461953629P | 2014-03-14 | 2014-03-14 | |
US61/953,629 | 2014-03-14 | ||
US201562107981P | 2015-01-26 | 2015-01-26 | |
US62/107,981 | 2015-01-26 | ||
US201562108476P | 2015-01-27 | 2015-01-27 | |
US62/108,476 | 2015-01-27 | ||
PCT/US2015/020783 WO2015139046A1 (en) | 2014-03-14 | 2015-03-16 | Methods and compositions for secretion of heterologous polypeptides |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020001218A Division JP2020078305A (ja) | 2014-03-14 | 2020-01-08 | 異種ポリペプチドを分泌させるための方法及び組成物 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2017510294A true JP2017510294A (ja) | 2017-04-13 |
JP2017510294A5 JP2017510294A5 (ja) | 2018-04-26 |
JP6644717B2 JP6644717B2 (ja) | 2020-02-12 |
Family
ID=52829322
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016575644A Active JP6644717B2 (ja) | 2014-03-14 | 2015-03-16 | 異種ポリペプチドを分泌させるための方法及び組成物 |
JP2020001218A Pending JP2020078305A (ja) | 2014-03-14 | 2020-01-08 | 異種ポリペプチドを分泌させるための方法及び組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020001218A Pending JP2020078305A (ja) | 2014-03-14 | 2020-01-08 | 異種ポリペプチドを分泌させるための方法及び組成物 |
Country Status (18)
Country | Link |
---|---|
US (2) | US10435694B2 (ja) |
EP (1) | EP3116999B1 (ja) |
JP (2) | JP6644717B2 (ja) |
KR (1) | KR102561695B1 (ja) |
CN (1) | CN106103730B (ja) |
AU (1) | AU2015229035B2 (ja) |
BR (1) | BR112016020822A2 (ja) |
CA (1) | CA2941687A1 (ja) |
ES (1) | ES2897765T3 (ja) |
HR (1) | HRP20211748T1 (ja) |
IL (1) | IL247632B (ja) |
MA (1) | MA39746A (ja) |
MX (2) | MX2016011637A (ja) |
PL (1) | PL3116999T3 (ja) |
RU (1) | RU2748026C2 (ja) |
SG (1) | SG11201607519VA (ja) |
SI (1) | SI3116999T1 (ja) |
WO (1) | WO2015139046A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020520670A (ja) * | 2017-05-24 | 2020-07-16 | ジーイー・ヘルスケア・バイオプロセス・アールアンドディ・アクチボラグ | 組換えタンパク質 |
JP2021511825A (ja) * | 2018-01-26 | 2021-05-13 | ヒューオンス カンパニー, リミテッドHuons Co., Ltd. | 二硫化結合異性化酵素信号ペプチドを含む組み換えベクターおよびその用途 |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2941687A1 (en) * | 2014-03-14 | 2015-09-17 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
WO2018081350A1 (en) * | 2016-10-27 | 2018-05-03 | Medimmune, Llc | Signal polypeptide for improved secretion of protein |
CN106676122B (zh) * | 2017-01-24 | 2019-10-29 | 成都分子脉象生物科技有限公司 | 一种基于AraF信号肽的双功能DNA元件及其应用 |
CN113454227A (zh) * | 2018-12-19 | 2021-09-28 | 维萨梅布有限公司 | 编码蛋白质的rna |
CN114829578A (zh) * | 2019-08-05 | 2022-07-29 | 瓦克化学股份公司 | 用于在发酵方法中释放重组蛋白的细菌菌株 |
WO2021158163A1 (en) * | 2020-02-07 | 2021-08-12 | Xbrane Biopharma Ab | Synthetically evolved dna constructs for regulating signal peptide performance as well as vectors, host cells and recombinant proteins thereof |
SE544059C2 (en) * | 2020-02-07 | 2021-11-30 | Cloneopt Ab | Synthetically evolved dna constructs for regulating signal peptide performance as well as vectors and host cells thereof |
SE543945C2 (en) * | 2020-02-07 | 2021-10-05 | Cloneopt Ab | Synthetically evolved DNA constructs for regulating signal peptide performance as well as vectors and host cells thereof |
WO2023046930A1 (en) * | 2021-09-24 | 2023-03-30 | Xbrane Biopharma Ab | Dna constructs and host cells for expressing recombinant protein |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010517532A (ja) * | 2007-01-31 | 2010-05-27 | ダウ グローバル テクノロジーズ インコーポレイティド | 発現上昇のための細菌リーダー配列 |
JP2013509867A (ja) * | 2009-11-05 | 2013-03-21 | ジェネンテック, インコーポレイテッド | 異種ポリペプチドの分泌のための方法及び組成物 |
Family Cites Families (125)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3645090A (en) | 1969-06-19 | 1972-02-29 | Citizen Watch Co Ltd | Day-date quick-adjuster for calender timepiece |
US3940475A (en) | 1970-06-11 | 1976-02-24 | Biological Developments, Inc. | Radioimmune method of assaying quantitatively for a hapten |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4675187A (en) | 1983-05-16 | 1987-06-23 | Bristol-Myers Company | BBM-1675, a new antibiotic complex |
US4737456A (en) | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
AU634186B2 (en) | 1988-11-11 | 1993-02-18 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5264365A (en) | 1990-11-09 | 1993-11-23 | Board Of Regents, The University Of Texas System | Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides |
US5508192A (en) | 1990-11-09 | 1996-04-16 | Board Of Regents, The University Of Texas System | Bacterial host strains for producing proteolytically sensitive polypeptides |
EP0564531B1 (en) | 1990-12-03 | 1998-03-25 | Genentech, Inc. | Enrichment method for variant proteins with altered binding properties |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
US6407213B1 (en) | 1991-06-14 | 2002-06-18 | Genentech, Inc. | Method for making humanized antibodies |
GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
WO1993006217A1 (en) | 1991-09-19 | 1993-04-01 | Genentech, Inc. | EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
DE69333807T2 (de) | 1992-02-06 | 2006-02-02 | Chiron Corp., Emeryville | Marker für krebs und biosynthetisches bindeprotein dafür |
CA2140280A1 (en) | 1992-08-17 | 1994-03-03 | Avi J. Ashkenazi | Bispecific immunoadhesins |
DK0669836T3 (da) | 1992-11-13 | 1996-10-14 | Idec Pharma Corp | Terapeutisk anvendelse af kimære og radioaktivt mærkede antistoffer og humant B-lymfocytbegrænset differentieringsantigen til behandling af B-cellelymfom |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
EP0714409A1 (en) | 1993-06-16 | 1996-06-05 | Celltech Therapeutics Limited | Antibodies |
DE4417598A1 (de) | 1994-05-19 | 1995-12-14 | Max Planck Gesellschaft | Verwendung des Tetracyclinpromotors zur stringent regulierten Produktion von rekombinanten Proteinen in prokaryontischen Zellen |
US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US5639635A (en) | 1994-11-03 | 1997-06-17 | Genentech, Inc. | Process for bacterial production of polypeptides |
US5747662A (en) | 1995-03-01 | 1998-05-05 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US6242177B1 (en) | 1995-03-01 | 2001-06-05 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5739277A (en) | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
GB9603256D0 (en) | 1996-02-16 | 1996-04-17 | Wellcome Found | Antibodies |
WO1997038123A1 (en) | 1996-04-05 | 1997-10-16 | Board Of Regents, The University Of Texas System | Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells |
IL132560A0 (en) | 1997-05-02 | 2001-03-19 | Genentech Inc | A method for making multispecific antibodies having heteromultimeric and common components |
US6083715A (en) | 1997-06-09 | 2000-07-04 | Board Of Regents, The University Of Texas System | Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells |
PT994903E (pt) | 1997-06-24 | 2005-10-31 | Genentech Inc | Metodos e composicoes para glicoproteinas galactosiladas |
WO1999022764A1 (en) | 1997-10-31 | 1999-05-14 | Genentech, Inc. | Methods and compositions comprising glycoprotein glycoforms |
US6610833B1 (en) | 1997-11-24 | 2003-08-26 | The Institute For Human Genetics And Biochemistry | Monoclonal human natural antibodies |
IL136544A0 (en) | 1997-12-05 | 2001-06-14 | Scripps Research Inst | Humanization of murine antibody |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
ES2532910T3 (es) | 1998-04-02 | 2015-04-01 | Genentech, Inc. | Variantes de anticuerpos y fragmentos de los mismos |
WO1999054342A1 (en) | 1998-04-20 | 1999-10-28 | Pablo Umana | Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
ES2694002T3 (es) | 1999-01-15 | 2018-12-17 | Genentech, Inc. | Polipéptido que comprende una región Fc de IgG1 humana variante |
ES2568899T3 (es) | 1999-04-09 | 2016-05-05 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de una molécula inmunofuncional |
CH694589A5 (de) | 1999-06-25 | 2005-04-15 | Genentech Inc | Humanisierte Anti-ErbB2-Antikörper und Behandlung mit Anti-ErbB2-Antikörpern. |
JP4668498B2 (ja) | 1999-10-19 | 2011-04-13 | 協和発酵キリン株式会社 | ポリペプチドの製造方法 |
AU784983B2 (en) | 1999-12-15 | 2006-08-17 | Genentech Inc. | Shotgun scanning, a combinatorial method for mapping functional protein epitopes |
US7608681B2 (en) | 1999-12-24 | 2009-10-27 | Genentech, Inc. | Methods and compositions for prolonging elimination half-times of bioactive compounds |
ES2274823T3 (es) | 1999-12-29 | 2007-06-01 | Immunogen, Inc. | Agentes cototoxicos que comprenden doxorrubicinas y daunorrubicinas y su utilizacion terapeutica. |
CA2395832A1 (en) | 2000-01-25 | 2001-08-02 | Genentech, Inc. | Liv-1 related protein, polynucleotides encoding the same and use thereof for treatment of cancer |
PL357939A1 (en) | 2000-04-11 | 2004-08-09 | Genentech, Inc. | Multivalent antibodies and uses therefor |
US20020022659A1 (en) * | 2000-07-19 | 2002-02-21 | Harris Gregory D. | Crystalline and salt forms of an HIV protease inhibitor |
ES2651952T3 (es) | 2000-10-06 | 2018-01-30 | Kyowa Hakko Kirin Co., Ltd. | Células que producen unas composiciones de anticuerpo |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
CA2430013C (en) | 2000-11-30 | 2011-11-22 | Medarex, Inc. | Transgenic transchromosomal rodents for making human antibodies |
PT1355919E (pt) | 2000-12-12 | 2011-03-02 | Medimmune Llc | Moléculas com semivida longa, composições que as contêm e suas utilizações |
IL156111A0 (en) | 2000-12-14 | 2003-12-23 | Genentech Inc | Bacterial host strains |
US6979556B2 (en) | 2000-12-14 | 2005-12-27 | Genentech, Inc. | Separate-cistron contructs for secretion of aglycosylated antibodies from prokaryotes |
AU2002245142B2 (en) | 2000-12-14 | 2007-07-05 | Genentech, Inc. | Prokaryotically produced antibodies and uses thereof |
HUP0700103A3 (en) | 2001-08-03 | 2012-09-28 | Glycart Biotechnology Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
EP1908769A1 (en) | 2001-08-27 | 2008-04-09 | Genentech, Inc. | A system for antibody expression and assembly |
MXPA04001566A (es) | 2001-08-27 | 2004-05-17 | Genentech Inc | Un sistema para expresion y ensamblado de anticuerpos. |
CN100423777C (zh) | 2001-10-25 | 2008-10-08 | 杰南技术公司 | 糖蛋白组合物 |
US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
AU2003236020B2 (en) | 2002-04-09 | 2009-03-19 | Kyowa Hakko Kirin Co., Ltd. | Cell with depression or deletion of the activity of protein participating in GDP-fucose transport |
US20050031613A1 (en) | 2002-04-09 | 2005-02-10 | Kazuyasu Nakamura | Therapeutic agent for patients having human FcgammaRIIIa |
CN1930288B (zh) | 2002-04-09 | 2012-08-08 | 协和发酵麒麟株式会社 | 基因组被修饰的细胞 |
EP1498491A4 (en) | 2002-04-09 | 2006-12-13 | Kyowa Hakko Kogyo Kk | METHOD FOR INCREASING THE ACTIVITY OF AN ANTIBODY COMPOSITION FOR BINDING TO THE FC GAMMA RECEPTOR IIIA |
WO2003085118A1 (fr) | 2002-04-09 | 2003-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Procede de production de composition anticorps |
JPWO2003084569A1 (ja) | 2002-04-09 | 2005-08-11 | 協和醗酵工業株式会社 | 抗体組成物含有医薬 |
JP4753578B2 (ja) | 2002-06-03 | 2011-08-24 | ジェネンテック, インコーポレイテッド | 合成抗体ファージライブラリー |
US7361740B2 (en) | 2002-10-15 | 2008-04-22 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
AU2003287345A1 (en) | 2002-10-31 | 2004-06-07 | Genentech, Inc. | Methods and compositions for increasing antibody production |
EP1944320A1 (en) | 2002-12-16 | 2008-07-16 | Genentech, Inc. | Immunoglobulin variants and uses thereof |
CA2510003A1 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
AU2004279742A1 (en) | 2003-10-08 | 2005-04-21 | Kyowa Hakko Kirin Co., Ltd. | Fused protein composition |
JPWO2005035778A1 (ja) | 2003-10-09 | 2006-12-21 | 協和醗酵工業株式会社 | α1,6−フコシルトランスフェラーゼの機能を抑制するRNAを用いた抗体組成物の製造法 |
KR100570422B1 (ko) * | 2003-10-16 | 2006-04-11 | 한미약품 주식회사 | 대장균 분비서열을 이용하여 항체 단편을 분비·생산하는 발현벡터 및 이를 이용하여 항체 단편을 대량 생산하는 방법 |
HUE038955T2 (hu) | 2003-11-05 | 2018-12-28 | Roche Glycart Ag | Antigén-kötõ molekulák fokozott Fc receptor-kötõ affinitással és effektor funkcióval |
SG10201701737XA (en) | 2003-11-06 | 2017-04-27 | Seattle Genetics Inc | Monomethylvaline compounds capable of conjugation to ligands |
WO2005053742A1 (ja) | 2003-12-04 | 2005-06-16 | Kyowa Hakko Kogyo Co., Ltd. | 抗体組成物を含有する医薬 |
ZA200604864B (en) * | 2003-12-19 | 2007-10-31 | Genentech Inc | Monovalent antibody fragments useful as therapeutics |
MXPA06011199A (es) | 2004-03-31 | 2007-04-16 | Genentech Inc | Anticuerpos anti-tgf-beta humanizados. |
US7785903B2 (en) | 2004-04-09 | 2010-08-31 | Genentech, Inc. | Variable domain library and uses |
ES2579805T3 (es) | 2004-09-23 | 2016-08-16 | Genentech, Inc. | Anticuerpos y conjugados modificados por ingeniería genética con cisteína |
EP1797182A2 (en) | 2004-10-05 | 2007-06-20 | Wyeth a Corporation of the State of Delaware | Methods and compositions for improving recombinant protein production |
RU2404193C2 (ru) | 2005-03-25 | 2010-11-20 | Дженентек, Инк. | Способ лечения опухоли у субъекта |
RU2412249C2 (ru) | 2005-07-08 | 2011-02-20 | Юниверсити Оф Цюрих | Фаговый дисплей с применением котрансляционной транслокации слитых полипептидов |
CN100475965C (zh) | 2005-07-22 | 2009-04-08 | 上海高科联合生物技术研发有限公司 | 一种大肠杆菌高效外分泌表达溶葡萄球菌酶的方法 |
WO2007056441A2 (en) | 2005-11-07 | 2007-05-18 | Genentech, Inc. | Binding polypeptides with diversified and consensus vh/vl hypervariable sequences |
EP1973951A2 (en) | 2005-12-02 | 2008-10-01 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
CA2651567A1 (en) | 2006-05-09 | 2007-11-22 | Genentech, Inc. | Binding polypeptides with optimized scaffolds |
EP2035456A1 (en) | 2006-06-22 | 2009-03-18 | Novo Nordisk A/S | Production of bispecific antibodies |
EP2471816A1 (en) | 2006-08-30 | 2012-07-04 | Genentech, Inc. | Multispecific antibodies |
US20080226635A1 (en) | 2006-12-22 | 2008-09-18 | Hans Koll | Antibodies against insulin-like growth factor I receptor and uses thereof |
WO2008089132A2 (en) | 2007-01-12 | 2008-07-24 | Cornell Research Foundation, Inc. | Genetic selection for protein folding and solubility in the bacterial periplasm |
CN100592373C (zh) | 2007-05-25 | 2010-02-24 | 群康科技(深圳)有限公司 | 液晶显示面板驱动装置及其驱动方法 |
WO2009021548A1 (en) * | 2007-08-10 | 2009-02-19 | Wacker Chemie Ag | Expression of full length igg and secretion into the culture medium of prokaryotic cells |
PL2235064T3 (pl) | 2008-01-07 | 2016-06-30 | Amgen Inc | Sposób otrzymywania cząsteczek przeciwciał z heterodimerycznymi fc z zastosowaniem kierujących efektów elektrostatycznych |
CA2716851A1 (en) | 2008-03-06 | 2009-09-11 | Genentech, Inc. | Combination therapy with c-met and egfr antagonists |
WO2010054010A1 (en) * | 2008-11-07 | 2010-05-14 | Fabrus Llc | Anti-dll4 antibodies and uses thereof |
EP2358909B1 (en) | 2008-11-17 | 2015-09-02 | Cornell University | A system useful for reporting protein-protein interactions in the bacterial periplasm |
GB0917647D0 (en) | 2009-10-08 | 2009-11-25 | Glaxosmithkline Biolog Sa | Expression system |
SG187886A1 (en) | 2010-08-31 | 2013-04-30 | Genentech Inc | Biomarkers and methods of treatment |
US20130004481A1 (en) | 2011-01-12 | 2013-01-03 | Boehringer Ingelheim International Gmbh | Anticancer therapy |
AR086823A1 (es) | 2011-06-30 | 2014-01-22 | Genentech Inc | Formulaciones de anticuerpo anti-c-met, metodos |
AU2012312515A1 (en) | 2011-09-19 | 2014-03-13 | Genentech, Inc. | Combination treatments comprising c-met antagonists and B-raf antagonists |
RU2014124842A (ru) | 2011-11-21 | 2015-12-27 | Дженентек, Инк. | Очистка анти-с-мет антител |
CA2941687A1 (en) | 2014-03-14 | 2015-09-17 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
-
2015
- 2015-03-16 CA CA2941687A patent/CA2941687A1/en active Pending
- 2015-03-16 US US15/125,548 patent/US10435694B2/en active Active
- 2015-03-16 WO PCT/US2015/020783 patent/WO2015139046A1/en active Application Filing
- 2015-03-16 BR BR112016020822A patent/BR112016020822A2/pt not_active Application Discontinuation
- 2015-03-16 RU RU2016140244A patent/RU2748026C2/ru active
- 2015-03-16 MA MA039746A patent/MA39746A/fr unknown
- 2015-03-16 MX MX2016011637A patent/MX2016011637A/es unknown
- 2015-03-16 PL PL15716209T patent/PL3116999T3/pl unknown
- 2015-03-16 JP JP2016575644A patent/JP6644717B2/ja active Active
- 2015-03-16 SI SI201531745T patent/SI3116999T1/sl unknown
- 2015-03-16 ES ES15716209T patent/ES2897765T3/es active Active
- 2015-03-16 AU AU2015229035A patent/AU2015229035B2/en active Active
- 2015-03-16 EP EP15716209.0A patent/EP3116999B1/en active Active
- 2015-03-16 HR HRP20211748TT patent/HRP20211748T1/hr unknown
- 2015-03-16 SG SG11201607519VA patent/SG11201607519VA/en unknown
- 2015-03-16 KR KR1020167028574A patent/KR102561695B1/ko active IP Right Grant
- 2015-03-16 CN CN201580013658.9A patent/CN106103730B/zh active Active
-
2016
- 2016-09-05 IL IL247632A patent/IL247632B/en active IP Right Grant
- 2016-09-08 MX MX2021001460A patent/MX2021001460A/es unknown
-
2019
- 2019-08-22 US US16/548,599 patent/US11390872B2/en active Active
-
2020
- 2020-01-08 JP JP2020001218A patent/JP2020078305A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010517532A (ja) * | 2007-01-31 | 2010-05-27 | ダウ グローバル テクノロジーズ インコーポレイティド | 発現上昇のための細菌リーダー配列 |
JP2013509867A (ja) * | 2009-11-05 | 2013-03-21 | ジェネンテック, インコーポレイテッド | 異種ポリペプチドの分泌のための方法及び組成物 |
Non-Patent Citations (1)
Title |
---|
J. BACTERIOL., vol. 187, no. 9, JPN6019005749, 2005, pages 2983 - 2991, ISSN: 0003981171 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020520670A (ja) * | 2017-05-24 | 2020-07-16 | ジーイー・ヘルスケア・バイオプロセス・アールアンドディ・アクチボラグ | 組換えタンパク質 |
JP2021511825A (ja) * | 2018-01-26 | 2021-05-13 | ヒューオンス カンパニー, リミテッドHuons Co., Ltd. | 二硫化結合異性化酵素信号ペプチドを含む組み換えベクターおよびその用途 |
JP7193552B2 (ja) | 2018-01-26 | 2022-12-20 | ヒューオンス カンパニー,リミテッド | 二硫化結合異性化酵素信号ペプチドを含む組み換えベクターおよびその用途 |
Also Published As
Publication number | Publication date |
---|---|
CN106103730B (zh) | 2021-06-08 |
US20200181625A1 (en) | 2020-06-11 |
RU2016140244A3 (ja) | 2019-05-22 |
US11390872B2 (en) | 2022-07-19 |
WO2015139046A1 (en) | 2015-09-17 |
AU2015229035B2 (en) | 2021-08-05 |
IL247632B (en) | 2021-02-28 |
US10435694B2 (en) | 2019-10-08 |
JP6644717B2 (ja) | 2020-02-12 |
HRP20211748T1 (hr) | 2022-02-18 |
AU2015229035A1 (en) | 2016-09-22 |
IL247632A0 (en) | 2016-11-30 |
MX2021001460A (es) | 2021-04-28 |
EP3116999B1 (en) | 2021-09-15 |
RU2016140244A (ru) | 2018-04-17 |
US20170029825A1 (en) | 2017-02-02 |
SI3116999T1 (sl) | 2021-12-31 |
PL3116999T3 (pl) | 2021-12-27 |
SG11201607519VA (en) | 2016-10-28 |
KR102561695B1 (ko) | 2023-07-28 |
JP2020078305A (ja) | 2020-05-28 |
KR20160134758A (ko) | 2016-11-23 |
MA39746A (fr) | 2021-04-28 |
MX2016011637A (es) | 2017-04-13 |
EP3116999A1 (en) | 2017-01-18 |
CN106103730A (zh) | 2016-11-09 |
RU2748026C2 (ru) | 2021-05-19 |
CA2941687A1 (en) | 2015-09-17 |
BR112016020822A2 (pt) | 2017-10-03 |
ES2897765T3 (es) | 2022-03-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11390872B2 (en) | Methods and compositions for secretion of heterologous polypeptides | |
TWI798179B (zh) | 多特異性抗體之純化 | |
KR101860963B1 (ko) | 이종다량체 단백질의 생산 | |
KR101913448B1 (ko) | Fc 변이체 및 그의 생산 방법 | |
JP6216321B2 (ja) | 二重特異性抗体の構築の改善 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180314 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180314 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190123 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190226 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190523 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190726 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191210 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200108 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6644717 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |