Identification of RO4597014, a glucokinase activator studied in the clinic for the treatment of type 2 diabetes

…, MT Dvorozniak, W Geng, P Gillespie…

Index: Qian, Yimin; Corbett, Wendy L.; Berthel, Steven J.; Choi, Duk Soon; Dvorozniak, Mark T.; Geng, Wanping; Gillespie, Paul; Guertin, Kevin R.; Haynes, Nancy-Ellen; Kester, Robert F.; Mennona, Francis A.; Moore, David; Racha, Jagdish; Radinov, Roumen; Sarabu, Ramakanth; Scott, Nathan R.; Grimsby, Joseph; Mallalieu, Navita L. ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 4 p. 414 - 418

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Citation Number: 5

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 ...