1427744-12-4Relevant articles and documents
Identification of RO4597014, a glucokinase activator studied in the clinic for the treatment of type 2 diabetes
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.
, p. 414 - 418 (2013/07/25)
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.