LCQ-908 is a potent and oral active diacylglycerol acyltransferase 1 (DGAT1) inhibitor, used as anti-obesity and anti-diabetic agents. DGAT-1 is recognized to catalyze the conversion of diacylglycerol and fatty acyl CoA to triacylglycerol, which is highly expressed in the small intestine and plays a key role in postprandial triglyceride synthesis. LCQ908 inhibited BCRP-mediated efflux activity in a dose-dependent fashion in a BCRP over-expressing human ovarian cancer cell line with an IC50 value of 5 μM[3]. LCQ908 inhibited OATP1B1, OATP1B3 (estradiol 17β glucuronide transport), and OAT3 (estrone 3 sulfate transport) activity in a concentration-dependent manner with estimated IC50 values of 1.66 ± 0.95 μM, 3.34 ± 0.64 μM, and 0.973 ± 0.11 μM, respectively[3]. LCQ908 was fond to suppress the postprandial triglyceride levels in rats, dogs as well as monkeys. LCQ908 decreased the postprandial rate of CM-TG secretion into the lymphatic duct and reduced the size of CMs[1]. In a clinical trial, LCQ908 was absorbed slowly, with a median tmax of ∼10 hours and eliminated slowly with a long half-life[4]. LCQ908 treatment led to dose-dependent suppression of postprandial triglyceride excursions over 9 hours following a high-fat meal test. In addition, LCQ908 suppressed postprandial glucose and insulin and increased plasma glucagon-like peptide-1 levels[4].
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