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• W2072332587 abstract "Diacylglycerol acyltransferase 2 (DGAT2), which catalyzes the final step in triacylglycerol (TG) synthesis, is a key enzyme associated with hepatic steatosis and insulin resistance. Here, using an in vitro screen of 20000 molecules, we identified a class of compounds with a substituted 1H-pyrrolo[2,3-b]pyridine core which proved to be potent and selective inhibitors of human DGAT2. Of these compounds, H2-003 and -005 exhibited a considerable reduction in TG biosynthesis in HepG2 hepatic cells and 3T3-L1 preadipose cells. These compounds exert DGAT2-specific-inhibitory activity, which was further confirmed in DGAT2- or DGAT1-overexpressing HEK293 cells. In addition, these compounds almost completely abolished lipid droplet formation in 3T3-L1 cells when co-treated with a DGAT1 inhibitor, which was not attained using either a DGAT2 or DGAT1 inhibitor alone. Collectively, we identified two DGAT2 inhibitors, H2-003 and -005. These compounds will aid in DGAT2-related lipid metabolism research as well as in therapeutic development for the treatment of metabolic diseases associated with excessive TG." @default.
• W2072332587 created "2016-06-24" @default.
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• W2072332587 date "2014-01-01" @default.
• W2072332587 modified "2023-10-17" @default.
• W2072332587 title "Discovery of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors with a 1<i>H</i>-Pyrrolo[2,3-<i>b</i>]pyridine Core" @default.
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• W2072332587 doi "https://doi.org/10.1248/bpb.b14-00447" @default.
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