SCD1 (stearoyl-CoA desaturase1) plays an important role in lipid metabolism and body weight control. Higher SCD1 activity in humans has been correlated with elevated plasma triglyceride levels. A939572 is an orally bioavailable and potent SCD1 inhibitor with IC50 values of <4 nM and 37 nM for mSCD1 and hSCD1, respectively [3]. A939572 demonstrated a significant dose-dependent decrease in proliferation in Caki1, A498, Caki2, and ACHN at day 5 (IC50s of 65 nM, 50 nM, 65 nM, and 6 nM respectively). Moreover, A939572 induced apoptosis in all four cell lines [4]. A939572 has modest volume of distribution and high oral bioavailability in mice (CLp= 0.4 L/h/kg; Vss= 0.4 L/kg; F= 92%). In ob/ob mice, A939572 (10 mpk bid) consistently reduced desaturation indices of all these lipid categories (cholesterol ester, diacylglycerol, free fatty acid, free cholesterol, total phospholipids, and triacylglycerol) to lean level, or even lower. A dose dependent triglyceride desaturation index reduction by A939572 was also observed in ob/ob mice [3].
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