Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for the Treatment of Type 2 Diabetes
ACS Medicinal Chemistry Letters2013Vol. 4(4), pp. 414–418
Citations Over TimeTop 16% of 2013 papers
Yimin Qian, Wendy L. Corbett, Steven J. Berthel, Duk Soon Choi, Mark Dvorozniak, Wanping Geng, Paul Gillespie, Kevin R. Guertin, Nancy-Ellen Haynes, Robert F. Kester, Francis A. Mennona, David Moore, Jagdish K. Racha, Roumen Radinov, Ramakanth Sarabu, Nathan R. Scott, Joseph Grimsby, Navita L. Mallalieu
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.
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