EA035088B1 - Анти-angptl8 антитела и их применение - Google Patents
Анти-angptl8 антитела и их применение Download PDFInfo
- Publication number
- EA035088B1 EA035088B1 EA201890453A EA201890453A EA035088B1 EA 035088 B1 EA035088 B1 EA 035088B1 EA 201890453 A EA201890453 A EA 201890453A EA 201890453 A EA201890453 A EA 201890453A EA 035088 B1 EA035088 B1 EA 035088B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- antibody
- angptl8
- antibodies
- amino acid
- seq
- Prior art date
Links
- 102100034604 Angiopoietin-like protein 8 Human genes 0.000 claims abstract description 158
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 76
- 238000000034 method Methods 0.000 claims abstract description 66
- 201000010099 disease Diseases 0.000 claims abstract description 58
- 101000924544 Homo sapiens Angiopoietin-like protein 8 Proteins 0.000 claims abstract description 48
- 102000050918 human ANGPTL8 Human genes 0.000 claims abstract description 36
- 210000004369 blood Anatomy 0.000 claims abstract description 30
- 239000008280 blood Substances 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 230000027455 binding Effects 0.000 claims description 210
- 239000012634 fragment Substances 0.000 claims description 122
- 239000000427 antigen Substances 0.000 claims description 119
- 108091007433 antigens Proteins 0.000 claims description 118
- 102000036639 antigens Human genes 0.000 claims description 118
- 150000003626 triacylglycerols Chemical class 0.000 claims description 66
- 230000000694 effects Effects 0.000 claims description 65
- 239000003814 drug Substances 0.000 claims description 40
- 108090000623 proteins and genes Proteins 0.000 claims description 40
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 39
- 102000004169 proteins and genes Human genes 0.000 claims description 39
- 102000039446 nucleic acids Human genes 0.000 claims description 36
- 108020004707 nucleic acids Proteins 0.000 claims description 36
- 150000007523 nucleic acids Chemical class 0.000 claims description 36
- 239000003112 inhibitor Substances 0.000 claims description 31
- 150000001413 amino acids Chemical group 0.000 claims description 30
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 229940124597 therapeutic agent Drugs 0.000 claims description 26
- 230000007423 decrease Effects 0.000 claims description 23
- 208000024891 symptom Diseases 0.000 claims description 21
- 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 claims description 18
- 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 claims description 18
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 16
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 16
- 241000282693 Cercopithecidae Species 0.000 claims description 15
- 239000005557 antagonist Substances 0.000 claims description 14
- 210000004027 cell Anatomy 0.000 claims description 14
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims description 14
- 102000045205 Angiopoietin-Like Protein 4 Human genes 0.000 claims description 10
- 102100025668 Angiopoietin-related protein 3 Human genes 0.000 claims description 10
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- -1 gliburide Chemical class 0.000 claims description 10
- 150000002632 lipids Chemical class 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229960003512 nicotinic acid Drugs 0.000 claims description 9
- 235000001968 nicotinic acid Nutrition 0.000 claims description 9
- 239000011664 nicotinic acid Substances 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 230000008859 change Effects 0.000 claims description 8
- 230000008030 elimination Effects 0.000 claims description 8
- 238000003379 elimination reaction Methods 0.000 claims description 8
- 102000006501 Angiopoietin-like Proteins Human genes 0.000 claims description 7
- 108010019425 Angiopoietin-like Proteins Proteins 0.000 claims description 7
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 7
- 239000003613 bile acid Substances 0.000 claims description 7
- 230000000903 blocking effect Effects 0.000 claims description 7
- 235000012000 cholesterol Nutrition 0.000 claims description 7
- 230000013595 glycosylation Effects 0.000 claims description 7
- 238000006206 glycosylation reaction Methods 0.000 claims description 7
- 238000007920 subcutaneous administration Methods 0.000 claims description 7
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 6
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 claims description 6
- 108010056301 Apolipoprotein C-III Proteins 0.000 claims description 6
- 102000030169 Apolipoprotein C-III Human genes 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 108010011459 Exenatide Proteins 0.000 claims description 6
- 108090001061 Insulin Proteins 0.000 claims description 6
- 102000004877 Insulin Human genes 0.000 claims description 6
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 6
- 108010019598 Liraglutide Proteins 0.000 claims description 6
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 6
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 6
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 6
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims description 6
- OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 claims description 6
- 229940125396 insulin Drugs 0.000 claims description 6
- 229960004844 lovastatin Drugs 0.000 claims description 6
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 6
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 6
- 108700027806 rGLP-1 Proteins 0.000 claims description 6
- 229960002855 simvastatin Drugs 0.000 claims description 6
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 6
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims description 6
- 229960001254 vildagliptin Drugs 0.000 claims description 6
- 102100034567 Angiopoietin-related protein 5 Human genes 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 claims description 5
- 101000924346 Homo sapiens Angiopoietin-related protein 5 Proteins 0.000 claims description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 108010005794 dulaglutide Proteins 0.000 claims description 5
- 239000013604 expression vector Substances 0.000 claims description 5
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 108010065920 Insulin Lispro Proteins 0.000 claims description 4
- 206010024604 Lipoatrophy Diseases 0.000 claims description 4
- 239000000556 agonist Substances 0.000 claims description 4
- 239000004026 insulin derivative Substances 0.000 claims description 4
- 238000003259 recombinant expression Methods 0.000 claims description 4
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 3
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 claims description 3
- GQPYTJVDPQTBQC-KLQYNRQASA-N (3r)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F GQPYTJVDPQTBQC-KLQYNRQASA-N 0.000 claims description 3
- RZPAXNJLEKLXNO-UKNNTIGFSA-N 22-Hydroxycholesterol 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)C(O)CCC(C)C)[C@@]1(C)CC2 RZPAXNJLEKLXNO-UKNNTIGFSA-N 0.000 claims description 3
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 3
- 229940127438 Amylin Agonists Drugs 0.000 claims description 3
- 206010002329 Aneurysm Diseases 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 102100034599 Angiopoietin-related protein 6 Human genes 0.000 claims description 3
- 108010024284 Apolipoprotein C-II Proteins 0.000 claims description 3
- 102000018616 Apolipoproteins B Human genes 0.000 claims description 3
- 108010027006 Apolipoproteins B Proteins 0.000 claims description 3
- 102000013918 Apolipoproteins E Human genes 0.000 claims description 3
- 108010025628 Apolipoproteins E Proteins 0.000 claims description 3
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 3
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 3
- 229940123208 Biguanide Drugs 0.000 claims description 3
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 3
- 229940122820 Cannabinoid receptor antagonist Drugs 0.000 claims description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
- 102000014914 Carrier Proteins Human genes 0.000 claims description 3
- 108010078791 Carrier Proteins Proteins 0.000 claims description 3
- 229920001268 Cholestyramine Polymers 0.000 claims description 3
- 229920002911 Colestipol Polymers 0.000 claims description 3
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 3
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 claims description 3
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims description 3
- 229940122904 Glucagon receptor antagonist Drugs 0.000 claims description 3
- 229940122853 Growth hormone antagonist Drugs 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 229940127336 Hormone Receptor Agonists Drugs 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 108010057186 Insulin Glargine Proteins 0.000 claims description 3
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 claims description 3
- 229940122355 Insulin sensitizer Drugs 0.000 claims description 3
- 238000008214 LDL Cholesterol Methods 0.000 claims description 3
- 206010049287 Lipodystrophy acquired Diseases 0.000 claims description 3
- XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 claims description 3
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 claims description 3
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 claims description 3
- 108010008364 Melanocortins Proteins 0.000 claims description 3
- 102000004316 Oxidoreductases Human genes 0.000 claims description 3
- 108090000854 Oxidoreductases Proteins 0.000 claims description 3
- 102000000536 PPAR gamma Human genes 0.000 claims description 3
- 108010016731 PPAR gamma Proteins 0.000 claims description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 3
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 claims description 3
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 claims description 3
- 229940100389 Sulfonylurea Drugs 0.000 claims description 3
- 229960002632 acarbose Drugs 0.000 claims description 3
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 3
- 239000012190 activator Substances 0.000 claims description 3
- 239000000048 adrenergic agonist Substances 0.000 claims description 3
- 229960004733 albiglutide Drugs 0.000 claims description 3
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 3
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 claims description 3
- 229940035676 analgesics Drugs 0.000 claims description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 3
- 239000003524 antilipemic agent Substances 0.000 claims description 3
- 230000000923 atherogenic effect Effects 0.000 claims description 3
- 229960005370 atorvastatin Drugs 0.000 claims description 3
- 239000003536 cannabinoid receptor antagonist Substances 0.000 claims description 3
- 150000001735 carboxylic acids Chemical class 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- 229960005110 cerivastatin Drugs 0.000 claims description 3
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical group COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 150000001840 cholesterol esters Chemical class 0.000 claims description 3
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 claims description 3
- 229960002604 colestipol Drugs 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 230000007812 deficiency Effects 0.000 claims description 3
- 235000005911 diet Nutrition 0.000 claims description 3
- 230000037213 diet Effects 0.000 claims description 3
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229960005175 dulaglutide Drugs 0.000 claims description 3
- 229960001519 exenatide Drugs 0.000 claims description 3
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims description 3
- 229960000815 ezetimibe Drugs 0.000 claims description 3
- 229940125753 fibrate Drugs 0.000 claims description 3
- 229960003765 fluvastatin Drugs 0.000 claims description 3
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 claims description 3
- 229960001381 glipizide Drugs 0.000 claims description 3
- 239000003862 glucocorticoid Substances 0.000 claims description 3
- 229960004717 insulin aspart Drugs 0.000 claims description 3
- 229960003948 insulin detemir Drugs 0.000 claims description 3
- 229960002869 insulin glargine Drugs 0.000 claims description 3
- 229960002068 insulin lispro Drugs 0.000 claims description 3
- 229940090473 januvia Drugs 0.000 claims description 3
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 claims description 3
- 208000006132 lipodystrophy Diseases 0.000 claims description 3
- 229960002701 liraglutide Drugs 0.000 claims description 3
- 229960001093 lixisenatide Drugs 0.000 claims description 3
- 108010004367 lixisenatide Proteins 0.000 claims description 3
- 239000002865 melanocortin Substances 0.000 claims description 3
- 229960003105 metformin Drugs 0.000 claims description 3
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 3
- 230000003472 neutralizing effect Effects 0.000 claims description 3
- VOMXSOIBEJBQNF-UTTRGDHVSA-N novorapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 claims description 3
- 229940012843 omega-3 fatty acid Drugs 0.000 claims description 3
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims description 3
- 229960005095 pioglitazone Drugs 0.000 claims description 3
- 229960002797 pitavastatin Drugs 0.000 claims description 3
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 3
- 229960003611 pramlintide Drugs 0.000 claims description 3
- 108010029667 pramlintide Proteins 0.000 claims description 3
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)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]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 claims description 3
- 229960002965 pravastatin Drugs 0.000 claims description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
- 229940076372 protein antagonist Drugs 0.000 claims description 3
- 239000003806 protein tyrosine phosphatase inhibitor Substances 0.000 claims description 3
- 229940044601 receptor agonist Drugs 0.000 claims description 3
- 239000000018 receptor agonist Substances 0.000 claims description 3
- 229960004586 rosiglitazone Drugs 0.000 claims description 3
- 229960000672 rosuvastatin Drugs 0.000 claims description 3
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 3
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 claims description 3
- 229960004937 saxagliptin Drugs 0.000 claims description 3
- 108010033693 saxagliptin Proteins 0.000 claims description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims description 3
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 3
- 229940035447 tanzeum Drugs 0.000 claims description 3
- CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical compound COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 claims description 3
- 229950004514 torcetrapib Drugs 0.000 claims description 3
- 229940007428 victoza Drugs 0.000 claims description 3
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 claims description 2
- ZXOCGDDVNPDRIW-NHFZGCSJSA-N Tofogliflozin Chemical compound O.C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZXOCGDDVNPDRIW-NHFZGCSJSA-N 0.000 claims description 2
- 229960001713 canagliflozin Drugs 0.000 claims description 2
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 229960003834 dapagliflozin Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229950006667 tofogliflozin Drugs 0.000 claims description 2
- 239000003102 growth factor Substances 0.000 claims 4
- 101710085848 Angiopoietin-related protein 3 Proteins 0.000 claims 2
- 101710085845 Angiopoietin-related protein 4 Proteins 0.000 claims 2
- 101710085819 Angiopoietin-related protein 6 Proteins 0.000 claims 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 1
- 108010051696 Growth Hormone Proteins 0.000 claims 1
- 102000018997 Growth Hormone Human genes 0.000 claims 1
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims 1
- 108010089308 Insulin Detemir Proteins 0.000 claims 1
- 229940122985 Peptide agonist Drugs 0.000 claims 1
- 102100040918 Pro-glucagon Human genes 0.000 claims 1
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 230000000202 analgesic effect Effects 0.000 claims 1
- 239000002308 endothelin receptor antagonist Substances 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 claims 1
- 239000000122 growth hormone Substances 0.000 claims 1
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 claims 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 1
- 239000003509 long acting drug Substances 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 239000003352 sequestering agent Substances 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 abstract description 22
- 208000035475 disorder Diseases 0.000 abstract description 18
- 108700041144 Angiopoietin-Like Protein 8 Proteins 0.000 description 150
- 125000003275 alpha amino acid group Chemical group 0.000 description 122
- 108090000765 processed proteins & peptides Proteins 0.000 description 71
- 102000004196 processed proteins & peptides Human genes 0.000 description 44
- 235000001014 amino acid Nutrition 0.000 description 37
- 235000018102 proteins Nutrition 0.000 description 35
- 210000002966 serum Anatomy 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 29
- 241000699670 Mus sp. Species 0.000 description 25
- 238000002347 injection Methods 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 230000004048 modification Effects 0.000 description 21
- 238000012986 modification Methods 0.000 description 21
- 229920001184 polypeptide Polymers 0.000 description 20
- 238000006467 substitution reaction Methods 0.000 description 19
- 238000010494 dissociation reaction Methods 0.000 description 18
- 230000005593 dissociations Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 17
- 102000043296 Lipoprotein lipases Human genes 0.000 description 17
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 101000693085 Homo sapiens Angiopoietin-related protein 3 Proteins 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 15
- 230000035772 mutation Effects 0.000 description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 239000011159 matrix material Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 230000002378 acidificating effect Effects 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 210000004897 n-terminal region Anatomy 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 125000003729 nucleotide group Chemical group 0.000 description 13
- 108060003951 Immunoglobulin Proteins 0.000 description 12
- 102000018358 immunoglobulin Human genes 0.000 description 12
- 230000007935 neutral effect Effects 0.000 description 12
- 108700042530 Angiopoietin-Like Protein 4 Proteins 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 11
- 239000000872 buffer Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 102000040430 polynucleotide Human genes 0.000 description 10
- 108091033319 polynucleotide Proteins 0.000 description 10
- 239000002157 polynucleotide Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 9
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 238000011577 humanized mouse model Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 101150054149 ANGPTL4 gene Proteins 0.000 description 8
- 206010014486 Elevated triglycerides Diseases 0.000 description 8
- 241000283707 Capra Species 0.000 description 7
- 230000002411 adverse Effects 0.000 description 7
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 229910052805 deuterium Inorganic materials 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 229940127121 immunoconjugate Drugs 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 230000003313 weakening effect Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 108020004511 Recombinant DNA Proteins 0.000 description 6
- 230000009102 absorption Effects 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 101000693076 Homo sapiens Angiopoietin-related protein 4 Proteins 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 101100042258 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) sem-1 gene Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 238000013270 controlled release Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 4
- AIRYAONNMGRCGJ-FHFVDXKLSA-N CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC AIRYAONNMGRCGJ-FHFVDXKLSA-N 0.000 description 4
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- 102000019267 Hepatic lipases Human genes 0.000 description 4
- 108050006747 Hepatic lipases Proteins 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 206010033645 Pancreatitis Diseases 0.000 description 4
- 206010033647 Pancreatitis acute Diseases 0.000 description 4
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
- 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 4
- 201000003229 acute pancreatitis Diseases 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 102000025171 antigen binding proteins Human genes 0.000 description 4
- 108091000831 antigen binding proteins Proteins 0.000 description 4
- 230000001906 cholesterol absorption Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 230000037356 lipid metabolism Effects 0.000 description 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 4
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000009103 reabsorption Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000010254 subcutaneous injection Methods 0.000 description 4
- 239000007929 subcutaneous injection Substances 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 101100042265 Caenorhabditis elegans sem-2 gene Proteins 0.000 description 3
- 102000051325 Glucagon Human genes 0.000 description 3
- 108060003199 Glucagon Proteins 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 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 3
- 229960004666 glucagon Drugs 0.000 description 3
- 102000053580 human ANGPTL3 Human genes 0.000 description 3
- 102000055659 human ANGPTL4 Human genes 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- ORMNNUPLFAPCFD-DVLYDCSHSA-M phenethicillin potassium Chemical compound [K+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C(C)OC1=CC=CC=C1 ORMNNUPLFAPCFD-DVLYDCSHSA-M 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 102220117530 rs112626848 Human genes 0.000 description 3
- 102220238658 rs1468529365 Human genes 0.000 description 3
- 102220268018 rs201210997 Human genes 0.000 description 3
- 238000009738 saturating Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- IJUQCWMZCMFFJP-GQSLRNSLSA-N 1-[(2R,4S,5R)-4-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-[hydroxy-[[(2R,3R,4R,5R)-3-hydroxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-sulfanylphosphoryl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound COCCO[C@@H]1[C@H](O)[C@@H](COP(O)(=S)O[C@@H]2[C@@H](COP(O)(=S)O[C@@H]3[C@@H](COP(O)(=S)O[C@@H]4[C@@H](COP(O)(=S)O[C@@H]5[C@@H](COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@@H]6[C@@H](COP(O)(=S)O[C@@H]7[C@@H](COP(O)(=S)O[C@@H]8[C@@H](COP(S)(=O)O[C@@H]9[C@@H](COP(O)(=S)O[C@@H]%10[C@@H](CO)O[C@H]([C@@H]%10OCCOC)n%10cnc%11c(N)ncnc%10%11)O[C@H]([C@@H]9OCCOC)n9cnc%10c9nc(N)[nH]c%10=O)O[C@H]([C@@H]8OCCOC)n8cc(C)c(N)nc8=O)O[C@H]([C@@H]7OCCOC)n7cc(C)c(=O)[nH]c7=O)O[C@H]([C@@H]6OCCOC)n6cc(C)c(=O)[nH]c6=O)n6cc(C)c(N)nc6=O)n6cc(C)c(=O)[nH]c6=O)n6cc(C)c(=O)[nH]c6=O)n6cnc7c6nc(N)[nH]c7=O)n6cc(C)c(=O)[nH]c6=O)n6cc(C)c(N)nc6=O)n6cc(C)c(N)nc6=O)n6cnc7c(N)ncnc67)n6cnc7c6nc(N)[nH]c7=O)n6cc(C)c(N)nc6=O)O[C@H]([C@@H]5OCCOC)n5cc(C)c(=O)[nH]c5=O)O[C@H]([C@@H]4OCCOC)n4cc(C)c(=O)[nH]c4=O)O[C@H]([C@@H]3OCCOC)n3cc(C)c(=O)[nH]c3=O)O[C@H]([C@@H]2OCCOC)n2cnc3c(N)ncnc23)O[C@H]1n1cc(C)c(=O)[nH]c1=O IJUQCWMZCMFFJP-GQSLRNSLSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 102100034159 Beta-3 adrenergic receptor Human genes 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108091008794 FGF receptors Proteins 0.000 description 2
- 206010059183 Familial hypertriglyceridaemia Diseases 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 101000924549 Homo sapiens Angiopoietin-related protein 6 Proteins 0.000 description 2
- 201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 2
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- 101710172072 Kexin Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 108090000787 Subtilisin Proteins 0.000 description 2
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 2
- MZZLGJHLQGUVPN-HAWMADMCSA-N anacetrapib Chemical compound COC1=CC(F)=C(C(C)C)C=C1C1=CC=C(C(F)(F)F)C=C1CN1C(=O)O[C@H](C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)[C@@H]1C MZZLGJHLQGUVPN-HAWMADMCSA-N 0.000 description 2
- 229950000285 anacetrapib Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000003178 anti-diabetic effect Effects 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229940009098 aspartate Drugs 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
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 description 2
- 229920000080 bile acid sequestrant Polymers 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 229950004181 dalcetrapib Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- DTMGIJFHGGCSLO-FIAQIACWSA-N ethyl (4z,7z,10z,13z,16z,19z)-docosa-4,7,10,13,16,19-hexaenoate;ethyl (5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenoate Chemical compound CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC.CCOC(=O)CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC DTMGIJFHGGCSLO-FIAQIACWSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000000556 factor analysis Methods 0.000 description 2
- 201000011110 familial lipoprotein lipase deficiency Diseases 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 229960004580 glibenclamide Drugs 0.000 description 2
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 208000020887 hyperlipoproteinemia type 3 Diseases 0.000 description 2
- 208000000522 hyperlipoproteinemia type IV Diseases 0.000 description 2
- 208000003532 hypothyroidism Diseases 0.000 description 2
- 230000002989 hypothyroidism Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 108010050259 insulin degludec Proteins 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- BNYHRGTXRPWASY-UHFFFAOYSA-N nonylsulfonylurea Chemical compound CCCCCCCCCS(=O)(=O)NC(N)=O BNYHRGTXRPWASY-UHFFFAOYSA-N 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000013610 patient sample Substances 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 102200148758 rs116840795 Human genes 0.000 description 2
- 230000000580 secretagogue effect Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000011301 standard therapy Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 229940013051 trulicity Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 229960001729 voglibose Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
- DWPVVZZGGGCRRM-UHFFFAOYSA-N (4-methoxyphenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCN(C)CC1 DWPVVZZGGGCRRM-UHFFFAOYSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 108010063919 Glucagon Receptors Proteins 0.000 description 1
- 102100040890 Glucagon receptor Human genes 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 229940094910 Insulin receptor antagonist Drugs 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical group C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 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 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
- 102000004882 Lipase Human genes 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 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
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000012736 aqueous medium 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
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 229940090047 auto-injector Drugs 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 238000012575 bio-layer interferometry Methods 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000001678 brown HT Substances 0.000 description 1
- SOEBTSCUOQNNLV-UHFFFAOYSA-N butyl n-(6-aminohexyl)carbamate Chemical compound CCCCOC(=O)NCCCCCCN SOEBTSCUOQNNLV-UHFFFAOYSA-N 0.000 description 1
- 102220349284 c.287A>T Human genes 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 229940015979 epipen Drugs 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229940038661 humalog Drugs 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000005305 interferometry Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229940028435 intralipid Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229950000991 ipragliflozin Drugs 0.000 description 1
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 235000019626 lipase activity Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000005257 nucleotidylation Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007030 peptide scission Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000012462 polypropylene substrate Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- QHGVXILFMXYDRS-UHFFFAOYSA-N pyraclofos Chemical compound C1=C(OP(=O)(OCC)SCCC)C=NN1C1=CC=C(Cl)C=C1 QHGVXILFMXYDRS-UHFFFAOYSA-N 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010223 real-time analysis Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 102220210869 rs1057524586 Human genes 0.000 description 1
- 102220220520 rs1060503090 Human genes 0.000 description 1
- 102220206698 rs142514490 Human genes 0.000 description 1
- 102220325921 rs1555376589 Human genes 0.000 description 1
- 102220142694 rs192332456 Human genes 0.000 description 1
- 102200164344 rs63751661 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000012154 short term therapy Methods 0.000 description 1
- 238000011524 similarity measure Methods 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000011830 transgenic mouse model 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
- 230000009452 underexpressoin Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 229950010266 volanesorsen Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39575—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from other living beings excluding bacteria and viruses, e.g. protozoa, fungi, plants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Mycology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Botany (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562202366P | 2015-08-07 | 2015-08-07 | |
| PCT/US2016/045535 WO2017027316A1 (en) | 2015-08-07 | 2016-08-04 | Anti-angptl8 antibodies and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201890453A1 EA201890453A1 (ru) | 2018-07-31 |
| EA035088B1 true EA035088B1 (ru) | 2020-04-27 |
Family
ID=56979626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201890453A EA035088B1 (ru) | 2015-08-07 | 2016-08-04 | Анти-angptl8 антитела и их применение |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US10259870B2 (enExample) |
| EP (1) | EP3331908B1 (enExample) |
| JP (2) | JP7141333B2 (enExample) |
| KR (1) | KR20180038020A (enExample) |
| CN (1) | CN107922478A (enExample) |
| AR (1) | AR105600A1 (enExample) |
| AU (1) | AU2016307430B2 (enExample) |
| CA (1) | CA2993976A1 (enExample) |
| EA (1) | EA035088B1 (enExample) |
| ES (1) | ES2870031T3 (enExample) |
| HK (1) | HK1250238A1 (enExample) |
| IL (1) | IL257263A (enExample) |
| MX (1) | MX394103B (enExample) |
| TW (1) | TW201713690A (enExample) |
| WO (1) | WO2017027316A1 (enExample) |
| ZA (1) | ZA201800352B (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR087329A1 (es) | 2011-06-17 | 2014-03-19 | Regeneron Pharma | Anticuerpos humanos contra proteina 3 de tipo angiopoietina humana |
| EP3201225B1 (en) * | 2014-10-03 | 2020-08-19 | NGM Biopharmaceuticals, Inc. | Angptl8 polypeptide and its use for treatment of conditions associated with elevated triglycerides |
| TW201713690A (zh) | 2015-08-07 | 2017-04-16 | 再生元醫藥公司 | 抗angptl8抗體及其用途 |
| WO2017142832A1 (en) * | 2016-02-17 | 2017-08-24 | Regeneron Pharmaceuticals, Inc. | Methods for treating or preventing atherosclerosis by administering an inhibitor of angptl3 |
| CA3016764A1 (en) | 2016-03-03 | 2017-09-08 | Regeneron Pharmaceuticals, Inc. | Methods for treating patients with hyperlipidemia by administering a pcsk9 inhibitor in combination with an angptl3 inhibitor |
| US11542332B2 (en) | 2016-03-26 | 2023-01-03 | Bioatla, Inc. | Anti-CTLA4 antibodies, antibody fragments, their immunoconjugates and uses thereof |
| MX386832B (es) * | 2016-04-08 | 2025-03-19 | Regeneron Pharma | Inhibidor angptl8 e inhibidor angptl3 para usarse en el tratamiento de hiperlipidemia. |
| MA45602A (fr) | 2016-07-08 | 2019-05-15 | Staten Biotechnology B V | Anticorps anti-apoc3 et leurs méthodes d'utilisation |
| CN110036029A (zh) * | 2016-11-17 | 2019-07-19 | 瑞泽恩制药公司 | 用抗angptl8抗体处理肥胖的方法 |
| JP6853716B2 (ja) * | 2017-03-31 | 2021-03-31 | 信越化学工業株式会社 | レジスト下層膜材料、パターン形成方法、及びレジスト下層膜形成方法 |
| JP2020517242A (ja) | 2017-04-21 | 2020-06-18 | スターテン・バイオテクノロジー・ベー・フェー | 抗ApoC3抗体およびその使用方法 |
| US11434303B2 (en) | 2017-06-28 | 2022-09-06 | Bluefin Biomedicine, Inc. | Anti-LY6H antibodies and antibody drug conjugates |
| US10538583B2 (en) | 2017-10-31 | 2020-01-21 | Staten Biotechnology B.V. | Anti-APOC3 antibodies and compositions thereof |
| MA50516A (fr) | 2017-10-31 | 2020-09-09 | Staten Biotechnology B V | Anticorps anti-apoc3 et leurs procédés d'utilisation |
| US10774139B2 (en) | 2017-11-10 | 2020-09-15 | Ngm Biopharmaceuticals, Inc. | ANGPTL8-binding agents and methods of use thereof |
| WO2019126194A1 (en) * | 2017-12-18 | 2019-06-27 | Regeneron Pharmaceuticals, Inc. | Angptl8 assay and uses thereof |
| WO2019173438A1 (en) * | 2018-03-06 | 2019-09-12 | Stc. Unm | Compositions and methods for reducing serum triglycerides |
| TWI747098B (zh) | 2018-12-21 | 2021-11-21 | 美商美國禮來大藥廠 | 抗angptl3/8複合物抗體及其使用方法 |
| EP3930753A4 (en) | 2019-02-26 | 2023-03-29 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID LIBRARIES FOR GLP1 RECEPTOR |
| EP4004051A4 (en) | 2019-07-19 | 2023-08-23 | Oncoresponse, Inc. | IMMUNOMODULATORY ANTIBODIES AND METHODS OF USE THEREOF |
| CN110613847B (zh) * | 2019-10-23 | 2022-02-11 | 北京市心肺血管疾病研究所 | 一种抑制血管生成素样蛋白8的物质的应用 |
| CN110694068A (zh) * | 2019-11-06 | 2020-01-17 | 北京市心肺血管疾病研究所 | 一种抑制血管生成素样蛋白8的物质的应用 |
| CN110694067A (zh) * | 2019-11-06 | 2020-01-17 | 首都医科大学附属北京安贞医院 | 一种抑制血管生成素样蛋白8的物质的应用 |
| CN111135303A (zh) * | 2020-01-17 | 2020-05-12 | 北京市心肺血管疾病研究所 | 一种抑制血管生成素样蛋白8的物质的应用 |
| KR20210095781A (ko) | 2020-01-24 | 2021-08-03 | 주식회사 에이프릴바이오 | 항원결합 단편 및 생리활성 이펙터 모이어티로 구성된 융합 컨스트럭트를 포함하는 다중결합항체 및 이를 포함하는 약학조성물 |
| KR20230074151A (ko) * | 2020-08-26 | 2023-05-26 | 트위스트 바이오사이언스 코포레이션 | Glp1r 변이체에 관한 방법 및 조성물 |
| CA3248667A1 (en) * | 2022-05-02 | 2023-11-09 | Novo Nordisk A/S | NEW ANTI-ANGIOPOETIN 3 TYPE ANTIBODIES SUITABLE FOR HIGH-CONCENTRATION COMPOSITIONS AND SUBCUTANEOUS ADMINISTRATION |
| WO2024069614A1 (en) * | 2022-09-30 | 2024-04-04 | 9163-0384 Québec Inc | Methods for the assessment of lipoprotein lipase deficiency and lipoprotein lipase bioavailability |
| CN119192369A (zh) * | 2023-06-25 | 2024-12-27 | 百奥泰生物制药股份有限公司 | 抗angptl3抗体及其应用 |
| CN119684452A (zh) * | 2024-12-25 | 2025-03-25 | 中国药科大学 | Angptl8中和性抗体在制备治疗细胞因子风暴综合征药物中的应用 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7368531B2 (en) | 1997-03-07 | 2008-05-06 | Human Genome Sciences, Inc. | Human secreted proteins |
| US20020132252A1 (en) | 1997-06-16 | 2002-09-19 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US7393663B2 (en) | 1997-08-01 | 2008-07-01 | Serono Genetics Institute S.A. | Expressed sequence tags and encoded human proteins |
| AU2577799A (en) | 1998-02-09 | 1999-08-23 | Human Genome Sciences, Inc. | 45 human secreted proteins |
| NZ523206A (en) | 1999-08-31 | 2004-12-24 | Genentech Inc | Antibodies that bind to tumor gene sequences |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| JP5848861B2 (ja) | 2004-04-20 | 2016-01-27 | ジェンマブ エー/エスGenmab A/S | Cd20に対するヒトモノクローナル抗体 |
| US7537903B2 (en) | 2007-04-23 | 2009-05-26 | Board Of Regents, The University Of Texas System | FGF21 upregulates expression of GLUT-1 in a βklotho-dependent manner |
| JP2010529954A (ja) | 2007-05-22 | 2010-09-02 | ノバルティス アーゲー | Fgf21関連障害を処置、診断および検出する方法 |
| EP2679234A3 (en) | 2009-12-02 | 2014-04-23 | Amgen Inc. | Binding proteins that bind to human FGFR1C, human beta-klotho and both human FGFR1C and human beta-klotho |
| JO3274B1 (ar) | 2009-12-24 | 2018-09-16 | Regeneron Pharma | أجسام مضادة بشرية للبروتين 4 المشابه لأجيوبيوتين البشري |
| US20120021409A1 (en) * | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| JO3756B1 (ar) | 2010-11-23 | 2021-01-31 | Regeneron Pharma | اجسام مضادة بشرية لمستقبلات الجلوكاجون |
| WO2012170977A1 (en) * | 2011-06-10 | 2012-12-13 | President And Fellows Of Harvard College | Modulation of pancreatic beta cell proliferation |
| AR087329A1 (es) | 2011-06-17 | 2014-03-19 | Regeneron Pharma | Anticuerpos humanos contra proteina 3 de tipo angiopoietina humana |
| WO2013106547A1 (en) * | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| AU2013237760A1 (en) * | 2012-10-08 | 2014-04-24 | Biotime, Inc. | Differentiated progeny of clonal progenitor cell lines |
| WO2014183207A1 (en) * | 2013-05-17 | 2014-11-20 | Exerkine Corporation | Therapeutic method of treating metabolic syndrome |
| CN104164451A (zh) * | 2014-08-09 | 2014-11-26 | 高连如 | 一种治疗2型糖尿病的基因工程干细胞 |
| EP3201225B1 (en) * | 2014-10-03 | 2020-08-19 | NGM Biopharmaceuticals, Inc. | Angptl8 polypeptide and its use for treatment of conditions associated with elevated triglycerides |
| TW201713690A (zh) | 2015-08-07 | 2017-04-16 | 再生元醫藥公司 | 抗angptl8抗體及其用途 |
| MX386832B (es) | 2016-04-08 | 2025-03-19 | Regeneron Pharma | Inhibidor angptl8 e inhibidor angptl3 para usarse en el tratamiento de hiperlipidemia. |
| CN110036029A (zh) | 2016-11-17 | 2019-07-19 | 瑞泽恩制药公司 | 用抗angptl8抗体处理肥胖的方法 |
-
2016
- 2016-07-29 TW TW105124009A patent/TW201713690A/zh unknown
- 2016-08-04 EA EA201890453A patent/EA035088B1/ru not_active IP Right Cessation
- 2016-08-04 ES ES16770103T patent/ES2870031T3/es active Active
- 2016-08-04 KR KR1020187006505A patent/KR20180038020A/ko not_active Withdrawn
- 2016-08-04 US US15/228,398 patent/US10259870B2/en active Active
- 2016-08-04 HK HK18109700.2A patent/HK1250238A1/zh unknown
- 2016-08-04 AR ARP160102386A patent/AR105600A1/es unknown
- 2016-08-04 EP EP16770103.6A patent/EP3331908B1/en active Active
- 2016-08-04 MX MX2018001532A patent/MX394103B/es unknown
- 2016-08-04 CA CA2993976A patent/CA2993976A1/en not_active Abandoned
- 2016-08-04 JP JP2018506347A patent/JP7141333B2/ja active Active
- 2016-08-04 WO PCT/US2016/045535 patent/WO2017027316A1/en not_active Ceased
- 2016-08-04 CN CN201680046225.8A patent/CN107922478A/zh active Pending
- 2016-08-04 AU AU2016307430A patent/AU2016307430B2/en not_active Ceased
-
2018
- 2018-01-18 ZA ZA2018/00352A patent/ZA201800352B/en unknown
- 2018-01-31 IL IL257263A patent/IL257263A/en unknown
-
2021
- 2021-03-04 JP JP2021034006A patent/JP2021090449A/ja active Pending
Non-Patent Citations (2)
| Title |
|---|
| Anonymous: "Product Data Sheet - Purified anti-Betatrophin (ANGPTL8)", BioLegend, 25 July 2014 (2014-07-25), XP002763965, Retrieved from the Internet: URL:http://www.biolegend.com/pop_pdf.php?id=10113, [retrieved on 2016-11-08], the whole document * |
| Zhang Ren: "OR13-6: A Monoclonal Neutralizing Antibody Against Lipasin (Angptl8), a Novel Lipid Regulator, Reduces Serum Triglycerides in Mice By Enhancing Lipoprotein Lipase-Mediated Triglyceride Clearance", ENDOCRINE SOCIETY'S 97TH ANNUAL MEETING AND EXPO, March 5-8, 2015 - SAN DIEGO CV Risk - Drugs, Sex, and Rock and Roll, 6 March 2015 (2015-03-06), XP002763964, DOI: 10.1210/endo-meetings.2015.DGM.3.OR13-6, Retrieved from the Internet: URL:http://press.endocrine.org/doi/10.1210/endo-meetings.2015.DGM.3.OR13-6, [retrieved on 2016-11-08], cited in the application, the whole document * |
Also Published As
| Publication number | Publication date |
|---|---|
| EA201890453A1 (ru) | 2018-07-31 |
| CA2993976A1 (en) | 2017-02-16 |
| KR20180038020A (ko) | 2018-04-13 |
| JP2021090449A (ja) | 2021-06-17 |
| IL257263A (en) | 2018-03-29 |
| TW201713690A (zh) | 2017-04-16 |
| MX394103B (es) | 2025-03-24 |
| AU2016307430B2 (en) | 2022-04-21 |
| JP7141333B2 (ja) | 2022-09-22 |
| JP2018525383A (ja) | 2018-09-06 |
| HK1250238A1 (zh) | 2018-12-07 |
| AR105600A1 (es) | 2017-10-18 |
| EP3331908A1 (en) | 2018-06-13 |
| ES2870031T3 (es) | 2021-10-26 |
| US20170037124A1 (en) | 2017-02-09 |
| US10259870B2 (en) | 2019-04-16 |
| CN107922478A (zh) | 2018-04-17 |
| MX2018001532A (es) | 2018-03-15 |
| EP3331908B1 (en) | 2021-03-10 |
| ZA201800352B (en) | 2018-12-19 |
| WO2017027316A1 (en) | 2017-02-16 |
| AU2016307430A1 (en) | 2018-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10259870B2 (en) | Anti-ANGPTL8 antibodies and uses thereof | |
| US20250066463A1 (en) | Methods for treating hyperlipidemia with an angptl8 inhibitor and an angptl3 inhibitor | |
| JP7759417B2 (ja) | レプチン受容体を活性化させる抗原結合タンパク質 | |
| US9657099B2 (en) | Anti-glucagon antibodies | |
| AU2017363143B2 (en) | Methods of treating obesity with anti-ANGPTL8 antibodies | |
| AU2011331998B2 (en) | Human antibodies to the glucagon receptor | |
| ES2699499T3 (es) | Anticuerpos anti-ANGPTL3 y usos de los mismos | |
| EA048830B1 (ru) | Полинуклеотиды, кодирующие антитела, которые связываются с лептиновым рецептором, и способ получения таких антител |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG TJ TM |
|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): RU |