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.) results in an almost complete inhibition of 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: Lowered total, VLDL, and LDL cholesterol and triglycerides dose dependently with 23%, 33%, 75%, and 62% reductions at 10 mg/kg/day.
In Vitro
CP-346086 (0.1-1000 nM) dose-dependently inhibits human MTP-mediated triglyceride transfer between vesicles with an IC50 of 2.0 nM[1]. CP-346086 (24 h) inhibits apolipoprotein B (apoB) and triglyceride secretion (IC50=2.6 nM) from Hep-G2 cells without affecting apoA-I secretion or lipid synthesis[1].
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Chandler CE, et, al. CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J Lipid Res. 2003 Oct;44(10):1887-901.
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