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• W2047101066 abstract "Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final committed step in the biosynthesis of triglycerides. DGAT-1 knockout mice have been shown to be resistant to diet-induced obesity and have increased insulin sensitivity. Thus, inhibition of DGAT-1 may represent an attractive target for the treatment of obesity or type II diabetes. Herein, we report the discovery and characterization of a potent and selective DGAT-1 inhibitor PF-04620110 (3). Compound 3 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of ≥0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, compound 3 has been advanced to human clinical studies." @default.
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• W2047101066 date "2011-03-18" @default.
• W2047101066 modified "2023-10-14" @default.
• W2047101066 title "Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1" @default.
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• W2047101066 doi "https://doi.org/10.1021/ml200051p" @default.
• W2047101066 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4018057" @default.
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