Anacetrapib 是CETP的抑制剂，能够抑制 rhCETP (IC50:7.9±2.5 nM) 和 C13S CETP 突变型 (IC50:11.8±1.9 nM) 的活性。

Anacetrapib (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.

Anacetrapib对巨噬细胞胆固醇逆向转运有促进作用,可增加30%的排泄物胆固醇含量.处理异常仓鼠模型,持续处理2周,与对照组相比,Anacetrapib （60 mg/kg/day）使CETP活性下降94%,HDL-胆固醇上升47%,不影响非HDL胆固醇浓度.与对照组相比,Anacetrapib处理的仓鼠HDL显示ABCG1和SR-B1调节的流出物增多. [14C]Anacetrapib（10 mg/kg,p.o.）给药48 h后,鼠和猴分别恢复～80和90%放射性,但排泄物中放射性几乎无变化.

Anacetrapib和抑制素联用时,既可提高HDL-胆固醇水平,也可降低LDL-胆固醇水平。Anacetrapib剂量依赖性地抑制CE从HDL3转变为HDL2。Anacetrapib对[14C]-dalcetrapibthiol与人类重组CETP的结合数无影响。

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].

875446-37-0

C30H25F10NO3

637.518

MK-0859;安塞曲匹

DMSO:117 mg/mL (183.5 mM)
Ethanol:57 mg/mL(89.4 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years