JP2016522163A5 - - Google Patents
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- JP2016522163A5 JP2016522163A5 JP2016505495A JP2016505495A JP2016522163A5 JP 2016522163 A5 JP2016522163 A5 JP 2016522163A5 JP 2016505495 A JP2016505495 A JP 2016505495A JP 2016505495 A JP2016505495 A JP 2016505495A JP 2016522163 A5 JP2016522163 A5 JP 2016522163A5
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- Japan
- Prior art keywords
- nrg4
- amino acid
- acid sequence
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- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 238000000034 method Methods 0.000 claims description 55
- 239000012634 fragment Substances 0.000 claims description 25
- 208000030159 metabolic disease Diseases 0.000 claims description 24
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 18
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 18
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 18
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 12
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- 102100022658 Pro-neuregulin-4, membrane-bound isoform Human genes 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 101001109767 Homo sapiens Pro-neuregulin-4, membrane-bound isoform Proteins 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 208000004930 Fatty Liver Diseases 0.000 claims description 6
- 206010016654 Fibrosis Diseases 0.000 claims description 6
- 208000030673 Homozygous familial hypercholesterolemia Diseases 0.000 claims description 6
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims description 6
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 230000007882 cirrhosis Effects 0.000 claims description 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 6
- 208000029078 coronary artery disease Diseases 0.000 claims description 6
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 6
- 201000001421 hyperglycemia Diseases 0.000 claims description 6
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 6
- 201000008980 hyperinsulinism Diseases 0.000 claims description 6
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 230000002028 premature Effects 0.000 claims description 6
- 210000000577 adipose tissue Anatomy 0.000 claims description 5
- 238000009825 accumulation Methods 0.000 claims description 4
- 239000003524 antilipemic agent Substances 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 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 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 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 claims description 3
- 239000008103 glucose Substances 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 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 2
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 claims description 2
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims description 2
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 claims description 2
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 102000004877 Insulin Human genes 0.000 claims description 2
- 108090001061 Insulin Proteins 0.000 claims description 2
- 101800002641 Neuregulin-4 Proteins 0.000 claims description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 229960005370 atorvastatin Drugs 0.000 claims description 2
- 229960000516 bezafibrate Drugs 0.000 claims description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 claims description 2
- 229960002174 ciprofibrate Drugs 0.000 claims description 2
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 claims description 2
- 229960001214 clofibrate Drugs 0.000 claims description 2
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims description 2
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims description 2
- 229960000815 ezetimibe Drugs 0.000 claims description 2
- 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 2
- 229960002297 fenofibrate Drugs 0.000 claims description 2
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 2
- 229960003765 fluvastatin Drugs 0.000 claims description 2
- 229960003627 gemfibrozil Drugs 0.000 claims description 2
- 229940125396 insulin Drugs 0.000 claims description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 2
- 229960003105 metformin Drugs 0.000 claims description 2
- 229960003512 nicotinic acid Drugs 0.000 claims description 2
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- 239000011664 nicotinic acid Substances 0.000 claims description 2
- 229960000672 rosuvastatin Drugs 0.000 claims description 2
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 2
- 229960002855 simvastatin Drugs 0.000 claims description 2
- 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 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 27
- 102000004169 proteins and genes Human genes 0.000 claims 11
- 108090000623 proteins and genes Proteins 0.000 claims 11
- 239000012491 analyte Substances 0.000 claims 2
- 230000004071 biological effect Effects 0.000 claims 2
- 230000000975 bioactive effect Effects 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 230000004060 metabolic process Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000003486 adipose tissue brown Anatomy 0.000 description 1
- 210000000593 adipose tissue white Anatomy 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361804046P | 2013-03-21 | 2013-03-21 | |
| US61/804,046 | 2013-03-21 | ||
| PCT/US2014/031171 WO2014153385A2 (en) | 2013-03-21 | 2014-03-19 | Methods of treating metabolic disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016522163A JP2016522163A (ja) | 2016-07-28 |
| JP2016522163A5 true JP2016522163A5 (enExample) | 2017-04-13 |
| JP6565121B2 JP6565121B2 (ja) | 2019-08-28 |
Family
ID=51581794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016505495A Expired - Fee Related JP6565121B2 (ja) | 2013-03-21 | 2014-03-19 | 代謝障害を治療する方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9878010B2 (enExample) |
| EP (1) | EP2976094B1 (enExample) |
| JP (1) | JP6565121B2 (enExample) |
| CN (1) | CN105228641A (enExample) |
| ES (1) | ES2751391T3 (enExample) |
| WO (1) | WO2014153385A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2744512B1 (en) | 2011-08-15 | 2019-07-03 | Children's Hospital Los Angeles | Use of neuregulin-4 for treatment of inflammatory bowel disease and necrotizing enterocolitis |
| AU2015336954A1 (en) * | 2014-10-22 | 2017-06-08 | Katholieke Universiteit Leuven Ku Leuven Research & Development | Modulating adipose tissue and adipogenesis |
| WO2016116477A1 (en) * | 2015-01-20 | 2016-07-28 | Universiteit Antwerpen | Neuregulin in the treatment of fibrotic disorders |
| WO2017058828A1 (en) | 2015-09-28 | 2017-04-06 | Children's Hospital Los Angeles | Methods for treating diseases mediated by erbb4-positive pro-inflammatory macrophages |
| WO2020086667A1 (en) * | 2018-10-25 | 2020-04-30 | American University | Method for promoting adipocyte differentiation and obesity-related disease treatment |
| AR121035A1 (es) | 2019-04-01 | 2022-04-13 | Lilly Co Eli | Compuestos de neuregulina-4 y métodos de uso |
| CN110279860A (zh) * | 2019-07-31 | 2019-09-27 | 上海交通大学医学院附属瑞金医院 | Nrg4作为靶点在制备糖尿病药物中的应用 |
| CN114075272B (zh) * | 2020-08-10 | 2023-09-22 | 杭州俊丰生物工程有限公司 | 一种人神经调节蛋白4的制备方法 |
| WO2024163874A2 (en) * | 2023-02-03 | 2024-08-08 | Avexegen Therapeutics, Inc. | Stable and controlled release formulations of neuregulin-4 analogs |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| US4366241A (en) | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
| US4517288A (en) | 1981-01-23 | 1985-05-14 | American Hospital Supply Corp. | Solid phase system for ligand assay |
| CA1291031C (en) | 1985-12-23 | 1991-10-22 | Nikolaas C.J. De Jaeger | Method for the detection of specific binding agents and their correspondingbindable substances |
| WO2001014415A2 (en) * | 1999-08-20 | 2001-03-01 | Chiron Corporation | Egfh2 genes and gene products |
| US7094882B2 (en) * | 2000-04-21 | 2006-08-22 | Yeda Research And Development Co. Ltd. | Growth factor which acts through erb b-4 rtk |
| US6544759B1 (en) * | 2000-04-21 | 2003-04-08 | Yeda Research And Development Co. Ltd | Polynucleotides encoding a novel growth factor which acts through ErbB-4 kinase receptor tyrosine |
| US7198899B2 (en) * | 2002-06-03 | 2007-04-03 | Chiron Corporation | Use of NRG4, or inhibitors thereof, in the treatment of colon and pancreatic cancers |
| US20050005622A1 (en) * | 2003-07-10 | 2005-01-13 | Powell Brian C. | Condiment holder |
| US20070015839A1 (en) * | 2005-07-14 | 2007-01-18 | Franco Folli | Daily Dosage Regimen for Treating Diabetes, Obesity, Metabolic Syndrome and Polycystic Ovary Syndrome |
| ES2315110B1 (es) * | 2006-07-14 | 2009-12-30 | Universidad De Barcelona | Compuestos para el tratamiento de enfermedades relacionadas con la resistencia a la insulina. |
| US20100303757A1 (en) * | 2009-05-29 | 2010-12-02 | Allergan, Inc. | Methods of Treating Chronic Neurogenic Inflammation Using Interleukin Retargeted Endopepidases |
| WO2012154987A1 (en) | 2011-05-10 | 2012-11-15 | Nestec Sa | Methods of disease activity profiling for personalized therapy management |
-
2014
- 2014-03-19 WO PCT/US2014/031171 patent/WO2014153385A2/en not_active Ceased
- 2014-03-19 US US14/778,379 patent/US9878010B2/en not_active Expired - Fee Related
- 2014-03-19 CN CN201480029386.7A patent/CN105228641A/zh active Pending
- 2014-03-19 JP JP2016505495A patent/JP6565121B2/ja not_active Expired - Fee Related
- 2014-03-19 ES ES14768873T patent/ES2751391T3/es active Active
- 2014-03-19 EP EP14768873.3A patent/EP2976094B1/en active Active
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