PCSK9-IN-13(compound 3f) is a potent PCSK9 inhibitor, which can antagonize low-density lipoprotein (LDL) receptor binding by binding to PCSK9, with an IC50 of 537 nM.
PCSK9-IN-13(compound 3f) (0.1 or 1 μM) restores LDL uptake in HepG2 hepatocytes in a dose-dependent manner[1].
PCSK9-IN-13(compound 3f) (3.28 or 16.4 mg/kg/day, s.c., 14 days) in male C57BL/6 mice dose not show a reduction in total cholesterol at a dose of 3.28 mg/kg, however, a dose of 16.4 mg/kg shows a significant reduction of total cholesterol plasma levels by approximately 10%, and exhibits excellent bioavailability[1].The pharmacokinetic parameters of PCSK9-IN-13(compound 3f) in C57BL/6 mice
References:
[1]. Benny J.Evison, et al. A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove.Bioorganic & Medicinal Chemistry