PF 06424439

PF-06424439 methanesulfonate is an oral, potent and selective imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitor with an IC50 of 14 nM[1]. PF-06424439 methanesulfonate is slowly reversible, time-dependent inhibitor, which inhibits DGAT2 in a noncompetitive mode with respect to the acyl-CoA substrate[2].

Research Areas >> Others

Signaling Pathways >> Metabolic Enzyme/Protease >> Acyltransferase

IC50: 14 nM (DGAT2)[1]

PF-06424439 methanesulfonate (p.o.; 60 mg/kg/day; for 3 days) reduces plasma TG and cholesterol levels and decreases nonsignificant in circulating lipids in mice (Ldlr-/-)[1]. PF-06424439 methanesulfonate (i.v.; 1 mg/kg) shows moderate clearance in rats following intravenous administration and moderate steady-state volume of distribution (Vdss) results in a short half-life[1]. Animal Model: Male low-density lipoprotein receptor (Ldlr) knockout mice (Ldlr-/-)[1] Dosage: 60 mg/kg Administration: P.o.; daily; for 3 days Result: Reduced plasma TG and cholesterol levels and decreased nonsignificant in circulating lipids. Animal Model: Male Wistar-Han rats[1] Dosage: 1 mg/kg Administration: I.v. Result: Showed moderate clearance and a short half-life with t1/2=1.39 h.

[1]. Futatsugi K, et al. Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2). J Med Chem. 2015 Sep 24;58(18):7173-85.

[2]. Pabst B, et al. Mechanistic Characterization of Long Residence Time Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2). Biochemistry. 2018 Dec 26;57(51):6997-7010.