Literature DB >> 24900686

Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for the Treatment of Type 2 Diabetes.

Yimin Qian1, Wendy L Corbett1, Steven J Berthel1, Duk Soon Choi1, Mark T Dvorozniak1, Wanping Geng1, Paul Gillespie1, Kevin R Guertin1, Nancy-Ellen Haynes1, Robert F Kester1, Francis A Mennona1, David Moore1, Jagdish Racha1, Roumen Radinov1, Ramakanth Sarabu1, Nathan R Scott1, Joseph Grimsby1, Navita L Mallalieu1.   

Abstract

To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.

Entities:  

Keywords:  Glucokinase activator; lipophilic ligand efficiency; metabolite; redox cycling; type 2 diabetes

Year:  2013        PMID： 24900686      PMCID： PMC4027226          DOI： 10.1021/ml400027y

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  13 in total

1.  Identification of novel and potent 2-amino benzamide derivatives as allosteric glucokinase activators.

Authors:  Teruyuki Nishimura; Tomoharu Iino; Morihiro Mitsuya; Makoto Bamba; Hitomi Watanabe; Daisuke Tsukahara; Kenji Kamata; Kaori Sasaki; Sumika Ohyama; Hideka Hosaka; Mayumi Futamura; Yasufumi Nagata; Jun-Ichi Eiki
Journal:  Bioorg Med Chem Lett       Date:  2009-01-21       Impact factor: 2.823

Review 2.  Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

Authors:  Nicholas A Meanwell
Journal:  Chem Res Toxicol       Date:  2011-07-26       Impact factor: 3.739

3.  Discovery of piragliatin--first glucokinase activator studied in type 2 diabetic patients.

Authors:  Ramakanth Sarabu; Fred T Bizzarro; Wendy L Corbett; Mark T Dvorozniak; Wanping Geng; Joseph F Grippo; Nancy-Ellen Haynes; Stanley Hutchings; Lisa Garofalo; Kevin R Guertin; Darryl W Hilliard; Marek Kabat; Robert F Kester; Wang Ka; Zhenmin Liang; Paige E Mahaney; Linda Marcus; Franz M Matschinsky; David Moore; Jagdish Racha; Roumen Radinov; Yi Ren; Lida Qi; Michael Pignatello; Cheryl L Spence; Thomas Steele; John Tengi; Joseph Grimsby
Journal:  J Med Chem       Date:  2012-08-01       Impact factor: 7.446

4.  Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus.

Authors:  Jeffrey A Pfefferkorn; Angel Guzman-Perez; John Litchfield; Robert Aiello; Judith L Treadway; John Pettersen; Martha L Minich; Kevin J Filipski; Christopher S Jones; Meihua Tu; Gary Aspnes; Hud Risley; Jianwei Bian; Benjamin D Stevens; Patricia Bourassa; Theresa D'Aquila; Levenia Baker; Nicole Barucci; Alan S Robertson; Francis Bourbonais; David R Derksen; Margit Macdougall; Over Cabrera; Jing Chen; Amanda Lee Lapworth; James A Landro; William J Zavadoski; Karen Atkinson; Nahor Haddish-Berhane; Beijing Tan; Lili Yao; Rachel E Kosa; Manthena V Varma; Bo Feng; David B Duignan; Ayman El-Kattan; Sharad Murdande; Shenping Liu; Mark Ammirati; John Knafels; Paul Dasilva-Jardine; Laurel Sweet; Spiros Liras; Timothy P Rolph
Journal:  J Med Chem       Date:  2012-01-24       Impact factor: 7.446

5.  Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675).

Authors:  Nancy-Ellen Haynes; Wendy L Corbett; Fred T Bizzarro; Kevin R Guertin; Darryl W Hilliard; George W Holland; Robert F Kester; Paige E Mahaney; Lida Qi; Cheryl L Spence; John Tengi; Mark T Dvorozniak; Aruna Railkar; Franz M Matschinsky; Joseph F Grippo; Joseph Grimsby; Ramakanth Sarabu
Journal:  J Med Chem       Date:  2010-05-13       Impact factor: 7.446

6.  Allosteric activators of glucokinase: potential role in diabetes therapy.

Authors:  Joseph Grimsby; Ramakanth Sarabu; Wendy L Corbett; Nancy-Ellen Haynes; Fred T Bizzarro; John W Coffey; Kevin R Guertin; Darryl W Hilliard; Robert F Kester; Paige E Mahaney; Linda Marcus; Lida Qi; Cheryl L Spence; John Tengi; Mark A Magnuson; Chang An Chu; Mark T Dvorozniak; Franz M Matschinsky; Joseph F Grippo
Journal:  Science       Date:  2003-07-18       Impact factor: 47.728

7.  SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: discovery of PSN-GK1.

Authors:  Lisa S Bertram; Daniel Black; Paul H Briner; Rosemary Chatfield; Andrew Cooke; Matthew C T Fyfe; P John Murray; Frédéric Naud; Masao Nawano; Martin J Procter; Günaj Rakipovski; Chrystelle M Rasamison; Christine Reynet; Karen L Schofield; Vilas K Shah; Felix Spindler; Amanda Taylor; Roy Turton; Geoffrey M Williams; Philippe Wong-Kai-In; Kosuke Yasuda
Journal:  J Med Chem       Date:  2008-06-28       Impact factor: 7.446

Review 8.  Assessing the potential of glucokinase activators in diabetes therapy.

Authors:  Franz M Matschinsky
Journal:  Nat Rev Drug Discov       Date:  2009-04-17       Impact factor: 84.694

9.  Investigation of functionally liver selective glucokinase activators for the treatment of type 2 diabetes.

Authors:  Gregory R Bebernitz; Valerie Beaulieu; Bethany A Dale; Richard Deacon; Alokesh Duttaroy; Jiaping Gao; Melissa S Grondine; Ramesh C Gupta; Mesut Kakmak; Michael Kavana; Louise C Kirman; Jinsheng Liang; Wieslawa M Maniara; Siralee Munshi; Sunil S Nadkarni; Herbert F Schuster; Travis Stams; Irene St Denny; Paul M Taslimi; Brian Vash; Shari L Caplan
Journal:  J Med Chem       Date:  2009-10-08       Impact factor: 7.446

10.  Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.

Authors:  Gary E Meininger; Russell Scott; Maria Alba; Yue Shentu; Edmund Luo; Himal Amin; Michael J Davies; Keith D Kaufman; Barry J Goldstein
Journal:  Diabetes Care       Date:  2011-10-12       Impact factor: 19.112
View more
  2 in total

1.  Design and Synthesis of Acetylenyl Benzamide Derivatives as Novel Glucokinase Activators for the Treatment of T2DM.

Authors:  Kaapjoo Park; Byoung Moon Lee; Kwan Hoon Hyun; Taedong Han; Dong Hoon Lee; Hyun Ho Choi
Journal:  ACS Med Chem Lett       Date:  2015-01-14       Impact factor: 4.345

2.  Palladium-catalyzed acetylation of arenes.

Authors:  Stephen D Ramgren; Neil K Garg
Journal:  Org Lett       Date:  2014-01-09       Impact factor: 6.005
  2 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.