CP-346086 is a highly potent and orally bioavailable inhibitor of microsomal triglyceride transfer protein (MTP), exhibiting an IC50 value of 2.0 nM against both human and rodent MTP. This compound effectively reduces plasma levels of cholesterol and triglycerides when administered in vivo.

MTP:2.0 nM (IC50)

CP-346086 (0.1-1000 nM) inhibits human MTP-mediated triglyceride transfer between vesicles in a dose-dependent manner with an IC50 of 2.0 nM[1], and after 24 hours, it inhibits apolipoprotein B (apoB) and triglyceride secretion (IC50 = 2.6 nM) from Hep-G2 cells without affecting apoA-I secretion or lipid synthesis[1].

CP-346086 (1-100 mg/kg; oral gavage once daily for 2 weeks) reduces plasma total, VLDL, and LDL cholesterol and triglycerides in mice[1]. CP-346086 (25 mg/kg; a single p.o.) almost completely inhibits Tyloxapol-induced triglyceride accumulation in fasted rats[1]. CP-346086 (0.1-10 mg/kg; a single p.o.) reduces acute plasma triglyceride in mice[1]. Animal Model: B6CBAF1J mice[1] Dosage: 1, 2, 10, 20, 100 mg/kg Administration: Oral gavage once daily for 2 weeks Result: Dose-dependent reductions in total, VLDL, and LDL cholesterol and triglycerides with 23%, 33%, 75%, and 62% reductions at 10 mg/kg/day.