Anacetrapib (MK-0859) (MK0859) is an effective, specific, reversible rhCETP and mutant CETP(C13S) inhibitor (IC50: 7.9 nM and 11.8 nM). Anacetrapib reduces the transfer of cholesteryl ester from HDL to LDL and/or VLDL thereby, producing an increase in serum HDL-cholesterol levels and a decrease in serum LDL-cholesterol levels.

CETP (recombinant human):7.9 nM, CETP (mutant, C13S):11.8 nM

Anacetrapib, in combination with inhibin, increased both HDL-cholesterol levels and decreased LDL-cholesterol levels.Anacetrapib dose-dependently inhibited the conversion of CE from HDL3 to HDL2.Anacetrapib had no effect on the number of [14C]-dalcetrapibthiol bindings to human recombinant CETP.Ki8751 also inhibited PDGFRα, c-Kit and FGFR-2, with higher IC50 values of 40 nM-170 nM. Effect.

Anacetrapib, in combination with inhibin, increased both HDL-cholesterol levels and decreased LDL-cholesterol levels.Anacetrapib dose-dependently inhibited the conversion of CE from HDL3 to HDL2.Anacetrapib had no effect on the number of [14C]-dalcetrapibthiol bindings to human recombinant CETP.Ki8751 also inhibited PDGFRα, c-Kit and FGFR-2, with higher IC50 values of 40 nM-170 nM. Effect.

The inhibitory potency (IC50) of Dalcetrapib, Torcetrapib, and Anacetrapib to decrease CE transfer from HDL to LDL by rhCETP and C13S CETP is measured using a scintillation proximity assay kit. Briefly, [3H]CE-labeled HDL donor particles are incubated in the presence of purified CETP proteins (final concentration 0.5 μg/mL) and biotinylated LDL acceptor particles for 3 h at 37°C. Subsequently, streptavidin-coupled polyvinyltoluene beads containing liquid scintillation cocktail binding selectively to biotinylated LDL are added, and the amount of [3H]CE molecules transferred to LDL is measured by β counting[1].

Anacetrapib (ANA) is dissolved in DMSO and diluted with appropriate media[2]. Cells are seeded in a 96 well plate overnight prior to the treatment by different concentrations of CETP inhibitors (e.g., Anacetrapib) for 24 h. Cell viability is measured using the CellTiter-Glo Luminescent Cell Viability Assay kit. Four wells are evaluated under each experimental condition[2].