azd7687

Description: AZD7687 is a novel, potent, selective, reversible and pyrazinecarboxamide-based inhibitor of diacylglycerol acyltransferase 1 (DGAT1) with an IC50 value of 80 nM for hDGAT1. AZD7687 attenuates postprandial triacylglyceride excursion. AZD7687 markedly reduced postprandial TAG excursion with a steep concentration-effect relationship. Incremental TAG AUC (area under the serum concentration vs. time curve) following SMM 60% was decreased > 75% from baseline at doses >=5 mg (p < 0.0001 vs. placebo). Serum levels of diacylglycerol, specifically measured with mass spectrometry, did not increase after AZD7687 administration. Nausea, vomiting and diarrhoea were reported with increasing doses and they limited dose escalation. Lowering of SMM fat content to 45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal symptoms at a given dose of AZD7687.

References: J Med Chem. 2012 Dec 13; 55(23):10610-29; Diabetes Obes Metab. 2013 Feb; 15(2):136-43.;