EA018037B1 - Способ повышения уровней эритроцитов - Google Patents

Info

Publication number

EA018037B1

EA018037B1 EA200970603A EA200970603A EA018037B1 EA 018037 B1 EA018037 B1 EA 018037B1 EA 200970603 A EA200970603 A EA 200970603A EA 200970603 A EA200970603 A EA 200970603A EA 018037 B1 EA018037 B1 EA 018037B1

Authority

EA

Eurasian Patent Office

Prior art keywords

amino acid

polypeptide

acid sequence

fusion protein

activin

Prior art date

2006-12-18

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 97
• 210000003743 erythrocyte Anatomy 0.000 title claims abstract description 90
• 230000001965 increasing effect Effects 0.000 title claims abstract description 18
• 102000001554 Hemoglobins Human genes 0.000 claims abstract description 39
• 108010054147 Hemoglobins Proteins 0.000 claims abstract description 39
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 300
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 292
• 229920001184 polypeptide Polymers 0.000 claims description 288
• 108090000623 proteins and genes Proteins 0.000 claims description 132
• 102000004169 proteins and genes Human genes 0.000 claims description 100
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 64
• 210000004027 cell Anatomy 0.000 claims description 52
• 108020001507 fusion proteins Proteins 0.000 claims description 49
• 102000037865 fusion proteins Human genes 0.000 claims description 49
• 150000001413 amino acids Chemical class 0.000 claims description 44
• 241000282414 Homo sapiens Species 0.000 claims description 34
• 208000007502 anemia Diseases 0.000 claims description 24
• 210000002966 serum Anatomy 0.000 claims description 24
• 239000003446 ligand Substances 0.000 claims description 22
• 230000015572 biosynthetic process Effects 0.000 claims description 20
• 239000003814 drug Substances 0.000 claims description 19
• 238000011282 treatment Methods 0.000 claims description 19
• 238000000746 purification Methods 0.000 claims description 13
• 229940079593 drug Drugs 0.000 claims description 12
• 210000001519 tissue Anatomy 0.000 claims description 12
• 230000019491 signal transduction Effects 0.000 claims description 9
• 210000004369 blood Anatomy 0.000 claims description 8
• 239000008280 blood Substances 0.000 claims description 8
• 150000002632 lipids Chemical class 0.000 claims description 7
• 108060003951 Immunoglobulin Proteins 0.000 claims description 6
• 238000010521 absorption reaction Methods 0.000 claims description 6
• 102000018358 immunoglobulin Human genes 0.000 claims description 6
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 5
• 208000020832 chronic kidney disease Diseases 0.000 claims description 5
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• 208000005652 acute fatty liver of pregnancy Diseases 0.000 claims description 4
• 238000009826 distribution Methods 0.000 claims description 4
• 108010085220 Multiprotein Complexes Proteins 0.000 claims description 3
• 102000007474 Multiprotein Complexes Human genes 0.000 claims description 3
• 102000007562 Serum Albumin Human genes 0.000 claims description 3
• 108010071390 Serum Albumin Proteins 0.000 claims description 3
• 125000000539 amino acid group Chemical group 0.000 claims description 3
• 230000004807 localization Effects 0.000 claims description 3
• 208000034578 Multiple myelomas Diseases 0.000 claims description 2
• 208000002903 Thalassemia Diseases 0.000 claims description 2
• 230000011664 signaling Effects 0.000 claims description 2
• 125000000524 functional group Chemical group 0.000 claims 2
• 230000000973 chemotherapeutic effect Effects 0.000 claims 1
• 210000002027 skeletal muscle Anatomy 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 37
• 241000288906 Primates Species 0.000 abstract description 4
• 241000283984 Rodentia Species 0.000 abstract description 4
• 241000251539 Vertebrata <Metazoa> Species 0.000 abstract description 4
• 108010059616 Activins Proteins 0.000 description 123
• 102000005606 Activins Human genes 0.000 description 123
• 239000000488 activin Substances 0.000 description 115
• 235000018102 proteins Nutrition 0.000 description 98
• 230000027455 binding Effects 0.000 description 68
• 150000001875 compounds Chemical class 0.000 description 56
• 239000005557 antagonist Substances 0.000 description 51
• 230000000694 effects Effects 0.000 description 51
• 150000007523 nucleic acids Chemical class 0.000 description 48
• 102000039446 nucleic acids Human genes 0.000 description 47
• 108020004707 nucleic acids Proteins 0.000 description 47
• 230000014509 gene expression Effects 0.000 description 38
• 235000001014 amino acid Nutrition 0.000 description 28
• 239000012634 fragment Substances 0.000 description 28
• 229940024606 amino acid Drugs 0.000 description 26
• 108020004414 DNA Proteins 0.000 description 24
• 102000003951 Erythropoietin Human genes 0.000 description 24
• 108090000394 Erythropoietin Proteins 0.000 description 24
• 229940105423 erythropoietin Drugs 0.000 description 24
• 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 24
• 239000013598 vector Substances 0.000 description 24
• -1 CC8P Chemical compound 0.000 description 21
• 210000001995 reticulocyte Anatomy 0.000 description 21
• 238000012360 testing method Methods 0.000 description 20
• 230000004927 fusion Effects 0.000 description 18
• 230000013595 glycosylation Effects 0.000 description 17
• 238000006206 glycosylation reaction Methods 0.000 description 17
• 239000002773 nucleotide Substances 0.000 description 17
• 125000003729 nucleotide group Chemical group 0.000 description 17
• 241000282412 Homo Species 0.000 description 16
• 102000005962 receptors Human genes 0.000 description 16
• 238000012216 screening Methods 0.000 description 16
• 108020003175 receptors Proteins 0.000 description 15
• 230000008859 change Effects 0.000 description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
• 108091033319 polynucleotide Proteins 0.000 description 14
• 102000040430 polynucleotide Human genes 0.000 description 14
• 239000002157 polynucleotide Substances 0.000 description 14
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 13
• 108091028043 Nucleic acid sequence Proteins 0.000 description 13
• 238000004519 manufacturing process Methods 0.000 description 13
• 230000004048 modification Effects 0.000 description 13
• 238000012986 modification Methods 0.000 description 13
• 239000000427 antigen Substances 0.000 description 12
• 108091007433 antigens Proteins 0.000 description 12
• 102000036639 antigens Human genes 0.000 description 12
• 239000003795 chemical substances by application Substances 0.000 description 12
• 238000005534 hematocrit Methods 0.000 description 12
• 230000035772 mutation Effects 0.000 description 12
• 239000013612 plasmid Substances 0.000 description 12
• 241000282693 Cercopithecidae Species 0.000 description 11
• 241000700605 Viruses Species 0.000 description 11
• 210000004408 hybridoma Anatomy 0.000 description 11
• 108010023082 activin A Proteins 0.000 description 10
• 230000010437 erythropoiesis Effects 0.000 description 10
• 230000001225 therapeutic effect Effects 0.000 description 10
• 241001465754 Metazoa Species 0.000 description 9
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 9
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 239000013604 expression vector Substances 0.000 description 9
• 239000002502 liposome Substances 0.000 description 9
• 239000008194 pharmaceutical composition Substances 0.000 description 9
• 239000002243 precursor Substances 0.000 description 9
• 230000001105 regulatory effect Effects 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 229960000187 tissue plasminogen activator Drugs 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• 210000000988 bone and bone Anatomy 0.000 description 8
• 230000003993 interaction Effects 0.000 description 8
• 230000007246 mechanism Effects 0.000 description 8
• 230000001404 mediated effect Effects 0.000 description 8
• 229940068196 placebo Drugs 0.000 description 8
• 239000000902 placebo Substances 0.000 description 8
• 230000004044 response Effects 0.000 description 8
• 230000001177 retroviral effect Effects 0.000 description 8
• 235000000346 sugar Nutrition 0.000 description 8
• 108010052946 Activin Receptors Proteins 0.000 description 7
• 241000699666 Mus <mouse, genus> Species 0.000 description 7
• 239000004473 Threonine Substances 0.000 description 7
• 210000001185 bone marrow Anatomy 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 238000012217 deletion Methods 0.000 description 7
• 230000037430 deletion Effects 0.000 description 7
• 231100000673 dose–response relationship Toxicity 0.000 description 7
• 210000003527 eukaryotic cell Anatomy 0.000 description 7
• 230000011132 hemopoiesis Effects 0.000 description 7
• 238000002703 mutagenesis Methods 0.000 description 7
• 231100000350 mutagenesis Toxicity 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 102000018918 Activin Receptors Human genes 0.000 description 6
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
• 241000282567 Macaca fascicularis Species 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
• 238000004820 blood count Methods 0.000 description 6
• 150000001720 carbohydrates Chemical group 0.000 description 6
• 230000000295 complement effect Effects 0.000 description 6
• 238000010276 construction Methods 0.000 description 6
• 230000001086 cytosolic effect Effects 0.000 description 6
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 210000004962 mammalian cell Anatomy 0.000 description 6
• 229910052760 oxygen Inorganic materials 0.000 description 6
• 239000001301 oxygen Substances 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• 108091026890 Coding region Proteins 0.000 description 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 108010076504 Protein Sorting Signals Proteins 0.000 description 5
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 230000000692 anti-sense effect Effects 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000004071 biological effect Effects 0.000 description 5
• 238000004140 cleaning Methods 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 239000003550 marker Substances 0.000 description 5
• 239000000816 peptidomimetic Substances 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 210000001236 prokaryotic cell Anatomy 0.000 description 5
• 238000000159 protein binding assay Methods 0.000 description 5
• 230000000087 stabilizing effect Effects 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• UBWXUGDQUBIEIZ-UHFFFAOYSA-N (13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-phenylpropanoate Chemical compound CC12CCC(C3CCC(=O)C=C3CC3)C3C1CCC2OC(=O)CCC1=CC=CC=C1 UBWXUGDQUBIEIZ-UHFFFAOYSA-N 0.000 description 4
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
• 241000699802 Cricetulus griseus Species 0.000 description 4
• 241000238631 Hexapoda Species 0.000 description 4
• 102000002746 Inhibins Human genes 0.000 description 4
• 108010004250 Inhibins Proteins 0.000 description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• 238000001042 affinity chromatography Methods 0.000 description 4
• 230000008485 antagonism Effects 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• 239000001506 calcium phosphate Substances 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 230000004069 differentiation Effects 0.000 description 4
• 238000010494 dissociation reaction Methods 0.000 description 4
• 230000005593 dissociations Effects 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 238000005516 engineering process Methods 0.000 description 4
• 230000002255 enzymatic effect Effects 0.000 description 4
• 235000019441 ethanol Nutrition 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 238000001415 gene therapy Methods 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 230000002163 immunogen Effects 0.000 description 4
• 230000001976 improved effect Effects 0.000 description 4
• 239000000893 inhibin Substances 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 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 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 210000003205 muscle Anatomy 0.000 description 4
• 230000006337 proteolytic cleavage Effects 0.000 description 4
• 238000010188 recombinant method Methods 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 150000008163 sugars Chemical class 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 230000008685 targeting Effects 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• 241000701447 unidentified baculovirus Species 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
• 102000014914 Carrier Proteins Human genes 0.000 description 3
• 102000053642 Catalytic RNA Human genes 0.000 description 3
• 108090000994 Catalytic RNA Proteins 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 102000016970 Follistatin Human genes 0.000 description 3
• 108010014612 Follistatin Proteins 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 108010024636 Glutathione Proteins 0.000 description 3
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• 108010036176 Melitten Proteins 0.000 description 3
• 101100460719 Mus musculus Noto gene Proteins 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• 108091034117 Oligonucleotide Proteins 0.000 description 3
• 229920002684 Sepharose Polymers 0.000 description 3
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 3
• 101100187345 Xenopus laevis noto gene Proteins 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 230000001195 anabolic effect Effects 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 210000000628 antibody-producing cell Anatomy 0.000 description 3
• 230000000890 antigenic effect Effects 0.000 description 3
• 108091008324 binding proteins Proteins 0.000 description 3
• 230000037182 bone density Effects 0.000 description 3
• 230000008468 bone growth Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 238000005277 cation exchange chromatography Methods 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 238000001246 colloidal dispersion Methods 0.000 description 3
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
• 235000018417 cysteine Nutrition 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• 229940088598 enzyme Drugs 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 229960003180 glutathione Drugs 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 239000003906 humectant Substances 0.000 description 3
• 238000009396 hybridization Methods 0.000 description 3
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
• 108020001756 ligand binding domains Proteins 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• VDXZNPDIRNWWCW-UHFFFAOYSA-N melitten Chemical compound NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-UHFFFAOYSA-N 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
• 150000003904 phospholipids Chemical class 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 229920002704 polyhistidine Polymers 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• 108091092562 ribozyme Proteins 0.000 description 3
• 150000003839 salts Chemical class 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 230000008054 signal transmission Effects 0.000 description 3
• 238000001542 size-exclusion chromatography Methods 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 210000000952 spleen Anatomy 0.000 description 3
• 210000000130 stem cell Anatomy 0.000 description 3
• 230000004936 stimulating effect Effects 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 102000035160 transmembrane proteins Human genes 0.000 description 3
• 108091005703 transmembrane proteins Proteins 0.000 description 3
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 208000030090 Acute Disease Diseases 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 108700028369 Alleles Proteins 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 241000256844 Apis mellifera Species 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 208000006386 Bone Resorption Diseases 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• 108020004705 Codon Proteins 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 241000196324 Embryophyta Species 0.000 description 2
• 108010013369 Enteropeptidase Proteins 0.000 description 2
• 102100029727 Enteropeptidase Human genes 0.000 description 2
• 241000206672 Gelidium Species 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
• 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
• 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
• 101710154606 Hemagglutinin Proteins 0.000 description 2
• 208000032843 Hemorrhage Diseases 0.000 description 2
• 102000008100 Human Serum Albumin Human genes 0.000 description 2
• 108091006905 Human Serum Albumin Proteins 0.000 description 2
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 101100448410 Mus musculus Gkn1 gene Proteins 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
• 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 101710176177 Protein A56 Proteins 0.000 description 2
• 101150023114 RNA1 gene Proteins 0.000 description 2
• 206010039491 Sarcoma 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
• 208000007536 Thrombosis Diseases 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 102000004357 Transferases Human genes 0.000 description 2
• 108090000992 Transferases Proteins 0.000 description 2
• 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 2
• 239000012190 activator Substances 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 238000007792 addition Methods 0.000 description 2
• 238000001261 affinity purification Methods 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 230000003042 antagnostic effect Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• GLGAUBPACOBAMV-DOFZRALJSA-N arachidonylcyclopropylamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NC1CC1 GLGAUBPACOBAMV-DOFZRALJSA-N 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 239000000090 biomarker Substances 0.000 description 2
• 208000034158 bleeding Diseases 0.000 description 2
• 230000000740 bleeding effect Effects 0.000 description 2
• 238000010322 bone marrow transplantation Methods 0.000 description 2
• 230000024279 bone resorption Effects 0.000 description 2
• 210000004900 c-terminal fragment Anatomy 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 239000006143 cell culture medium Substances 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000004821 effect on bone Effects 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 230000005714 functional activity Effects 0.000 description 2
• 238000005227 gel permeation chromatography Methods 0.000 description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
• 150000002333 glycines Chemical class 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000005090 green fluorescent protein Substances 0.000 description 2
• 239000000185 hemagglutinin Substances 0.000 description 2
• 230000002489 hematologic effect Effects 0.000 description 2
• 238000013537 high throughput screening Methods 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 210000005260 human cell Anatomy 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 230000003053 immunization Effects 0.000 description 2
• 238000002649 immunization Methods 0.000 description 2
• 238000003018 immunoassay Methods 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 229910052742 iron Inorganic materials 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 238000005304 joining Methods 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000010534 mechanism of action Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 239000000693 micelle Substances 0.000 description 2
• 201000000050 myeloid neoplasm Diseases 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 229920000747 poly(lactic acid) Polymers 0.000 description 2
• 239000004626 polylactic acid Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 102000054765 polymorphisms of proteins Human genes 0.000 description 2
• 230000001323 posttranslational effect Effects 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 238000003259 recombinant expression Methods 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 238000009738 saturating Methods 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 238000002864 sequence alignment Methods 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000001509 sodium citrate Substances 0.000 description 2
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 239000007790 solid phase Substances 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 238000001890 transfection Methods 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• 238000011269 treatment regimen Methods 0.000 description 2
• 229940078499 tricalcium phosphate Drugs 0.000 description 2
• 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
• 235000019731 tricalcium phosphate Nutrition 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 241001430294 unidentified retrovirus Species 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
• NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
• TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
• JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical class OC1CCCO1 JNODDICFTDYODH-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
• OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 102000013563 Acid Phosphatase Human genes 0.000 description 1
• 108010051457 Acid Phosphatase Proteins 0.000 description 1
• 102100024394 Adipocyte enhancer-binding protein 1 Human genes 0.000 description 1
• 208000007848 Alcoholism Diseases 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 239000004382 Amylase Substances 0.000 description 1
• 102000013142 Amylases Human genes 0.000 description 1
• 108010065511 Amylases Proteins 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 206010002961 Aplasia Diseases 0.000 description 1
• 108091023037 Aptamer Proteins 0.000 description 1
• 235000017060 Arachis glabrata Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000018262 Arachis monticola Nutrition 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 241000714235 Avian retrovirus Species 0.000 description 1
• 208000000412 Avitaminosis Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• 102100028726 Bone morphogenetic protein 10 Human genes 0.000 description 1
• 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
• 241000283725 Bos Species 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 241000701822 Bovine papillomavirus Species 0.000 description 1
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 102000012422 Collagen Type I Human genes 0.000 description 1
• 108010022452 Collagen Type I Proteins 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 201000006306 Cor pulmonale Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 241000701022 Cytomegalovirus Species 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
• 101100179813 Drosophila melanogaster Actbeta gene Proteins 0.000 description 1
• 101100291267 Drosophila melanogaster Miga gene Proteins 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 description 1
• 241000701959 Escherichia virus Lambda Species 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010074860 Factor Xa Proteins 0.000 description 1
• 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
• 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
• 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
• ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 229930186217 Glycolipid Natural products 0.000 description 1
• 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 1
• 101150057184 Gtpbp4 gene Proteins 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000833122 Homo sapiens Adipocyte enhancer-binding protein 1 Proteins 0.000 description 1
• 101000695367 Homo sapiens Bone morphogenetic protein 10 Proteins 0.000 description 1
• 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 1
• 101001090860 Homo sapiens Myeloblastin Proteins 0.000 description 1
• 101000701405 Homo sapiens Serine/threonine-protein kinase 36 Proteins 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical group O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• 201000002980 Hyperparathyroidism Diseases 0.000 description 1
• 206010062767 Hypophysitis Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 229940122526 Inhibin inhibitor Drugs 0.000 description 1
• 206010022971 Iron Deficiencies Diseases 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-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
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 206010024305 Leukaemia monocytic Diseases 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 102000043129 MHC class I family Human genes 0.000 description 1
• 108091054437 MHC class I family Proteins 0.000 description 1
• 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 239000004909 Moisturizer Substances 0.000 description 1
• 101100182721 Mus musculus Ly6e gene Proteins 0.000 description 1
• 101100354849 Mus musculus Pc gene Proteins 0.000 description 1
• 208000007101 Muscle Cramp Diseases 0.000 description 1
• 102100034681 Myeloblastin Human genes 0.000 description 1
• 108010056852 Myostatin Proteins 0.000 description 1
• 241001181114 Neta Species 0.000 description 1
• 101100395423 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) hog-1 gene Proteins 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 230000004989 O-glycosylation Effects 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010031252 Osteomyelitis Diseases 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 101150054854 POU1F1 gene Proteins 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 208000008601 Polycythemia Diseases 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 101800004937 Protein C Proteins 0.000 description 1
• 102000017975 Protein C Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• 101800001700 Saposin-D Proteins 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 208000005392 Spasm Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 108700005078 Synthetic Genes Proteins 0.000 description 1
• 101710137500 T7 RNA polymerase Proteins 0.000 description 1
• 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 1
• 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• 102100036407 Thioredoxin Human genes 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 108700009124 Transcription Initiation Site Proteins 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• 102000002138 Type I Activin Receptors Human genes 0.000 description 1
• 108010015920 Type I Activin Receptors Proteins 0.000 description 1
• 102000000523 Type II Activin Receptors Human genes 0.000 description 1
• 108010041546 Type II Activin Receptors Proteins 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 241000700647 Variola virus Species 0.000 description 1
• 206010047627 Vitamin deficiencies Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 108010023079 activin B Proteins 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 230000011759 adipose tissue development Effects 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 238000012867 alanine scanning Methods 0.000 description 1
• 206010001584 alcohol abuse Diseases 0.000 description 1
• 208000025746 alcohol use disease Diseases 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• 150000004645 aluminates Chemical class 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 235000019418 amylase Nutrition 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 238000005571 anion exchange chromatography Methods 0.000 description 1
• 229940069428 antacid Drugs 0.000 description 1
• 239000003159 antacid agent Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000001458 anti-acid effect Effects 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 230000002788 anti-peptide Effects 0.000 description 1
• 230000005875 antibody response Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 230000009831 antigen interaction Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 239000000823 artificial membrane Substances 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 102000005936 beta-Galactosidase Human genes 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000003462 bioceramic Substances 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• XFWJKVMFIVXPKK-UHFFFAOYSA-N calcium;oxido(oxo)alumane Chemical compound [Ca+2].[O-][Al]=O.[O-][Al]=O XFWJKVMFIVXPKK-UHFFFAOYSA-N 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 238000005251 capillar electrophoresis Methods 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 230000021523 carboxylation Effects 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 230000022159 cartilage development Effects 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 210000004671 cell-free system Anatomy 0.000 description 1
• 230000007248 cellular mechanism Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 230000007541 cellular toxicity Effects 0.000 description 1
• 229910010293 ceramic material Inorganic materials 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 229930183167 cerebroside Natural products 0.000 description 1
• 150000001784 cerebrosides Chemical class 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 230000015271 coagulation Effects 0.000 description 1
• 238000005345 coagulation Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229910017052 cobalt Inorganic materials 0.000 description 1
• 239000010941 cobalt Substances 0.000 description 1
• GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
• 239000000084 colloidal system Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002742 combinatorial mutagenesis Methods 0.000 description 1
• 230000001447 compensatory effect Effects 0.000 description 1
• 230000009918 complex formation Effects 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 239000003431 cross linking reagent Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 101150044395 dda1 gene Proteins 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
• SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 210000002257 embryonic structure Anatomy 0.000 description 1
• 208000028208 end stage renal disease Diseases 0.000 description 1
• 201000000523 end stage renal failure Diseases 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 230000000925 erythroid effect Effects 0.000 description 1
• 230000000913 erythropoietic effect Effects 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 230000005713 exacerbation Effects 0.000 description 1
• 238000002270 exclusion chromatography Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 239000000194 fatty acid Chemical class 0.000 description 1
• 229930195729 fatty acid Chemical class 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000012953 feeding on blood of other organism Effects 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 238000002875 fluorescence polarization Methods 0.000 description 1
• 108091006047 fluorescent proteins Proteins 0.000 description 1
• 102000034287 fluorescent proteins Human genes 0.000 description 1
• 229940028334 follicle stimulating hormone Drugs 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 150000002270 gangliosides Chemical class 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 150000004676 glycans Polymers 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 230000002414 glycolytic effect Effects 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 208000034737 hemoglobinopathy Diseases 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 235000012907 honey Nutrition 0.000 description 1
• 102000053342 human STK36 Human genes 0.000 description 1
• 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 201000009939 hypertensive encephalopathy Diseases 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 238000001114 immunoprecipitation Methods 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 208000018337 inherited hemoglobinopathy Diseases 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 201000002313 intestinal cancer Diseases 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 229910052746 lanthanum Inorganic materials 0.000 description 1
• 238000002386 leaching Methods 0.000 description 1
• 229910052745 lead Inorganic materials 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 230000029226 lipidation Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000007791 liquid phase Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000005291 magnetic effect Effects 0.000 description 1
• 201000004792 malaria Diseases 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000013011 mating Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 210000003716 mesoderm Anatomy 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 125000001360 methionine group Chemical class N[C@@H](CCSC)C(=O)* 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 230000001333 moisturizer Effects 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 201000006894 monocytic leukemia Diseases 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 108700039855 mouse a Proteins 0.000 description 1
• 230000037257 muscle growth Effects 0.000 description 1
• 231100000219 mutagenic Toxicity 0.000 description 1
• 230000003505 mutagenic effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 229950006780 n-acetylglucosamine Drugs 0.000 description 1
• 239000002088 nanocapsule Substances 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 230000004766 neurogenesis Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 108091008104 nucleic acid aptamers Proteins 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 210000000287 oocyte Anatomy 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 210000003463 organelle Anatomy 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 230000011164 ossification Effects 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 235000020232 peanut Nutrition 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 210000003800 pharynx Anatomy 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 125000001095 phosphatidyl group Chemical group 0.000 description 1
• 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 210000003635 pituitary gland Anatomy 0.000 description 1
• 230000003169 placental effect Effects 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 150000004804 polysaccharides Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 230000008092 positive effect Effects 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 229960000856 protein c Drugs 0.000 description 1
• 230000009145 protein modification Effects 0.000 description 1
• 108020001775 protein parts Proteins 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 238000004445 quantitative analysis Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 210000003705 ribosome Anatomy 0.000 description 1
• 102200158977 rs116107386 Human genes 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 208000007056 sickle cell anemia Diseases 0.000 description 1
• 230000037432 silent mutation Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 230000022379 skeletal muscle tissue development Effects 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 210000001082 somatic cell Anatomy 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 150000003408 sphingolipids Chemical class 0.000 description 1
• 210000004989 spleen cell Anatomy 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 201000009032 substance abuse Diseases 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 108060008226 thioredoxin Proteins 0.000 description 1
• 229940094937 thioredoxin Drugs 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 230000025366 tissue development Effects 0.000 description 1
• 230000008467 tissue growth Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000005030 transcription termination Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 230000010474 transient expression Effects 0.000 description 1
• 230000032258 transport Effects 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
• 238000010396 two-hybrid screening Methods 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 238000000108 ultra-filtration Methods 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 238000002562 urinalysis Methods 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 229960004295 valine Drugs 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 210000002845 virion Anatomy 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1