Anacetrapib

• Catalog No.: S2748
• CAS Number: 875446-37-0
• M. F.: C30H25F10NO3
• M. W.: 637.508432
• Storage: -20°C

SYNONYMS

• IUPAC name: (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({2-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-5-(trifluoromethyl)phenyl}methyl)-4-methyl-1,3-oxazolidin-2-one
• IUPAC Traditional name: anacetrapib
• Synonyms: MK-0859

DATABASE IDS

• CAS Number: 875446-37-0

PROPERTIES

• Salt Data: Free Base
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Hyperlipidaemia, Hypercholesterolaemia , Atherosclerosis

Biological Activity

• Description: Anacetrapib (MK0859) is a potent and selective rhCETP and mutant CETP(C13S) inhibitor with IC50 of 7.9 nM and 11.8 nM, respectively
• Targets: rhCETP; Mutant CETP (C13S)
• IC50: 7.9 nM; 11.8 nM ^[1]
• In Vitro: Anacetrapib is not only able to increase HDL-cholesterol, but also further decreases LDL-cholesterol when taken in combination with a statin. Anacetrapib dose-dependently and significantly decreases the transfer of CE from HDL3 to HDL2. Anacetrapib doesn’t affect the amount of [^14C]-dalcetrapibthiol bound to rhCETP. Anacetrapib decreases pre-β-HDL formation by more than 46%. ^[1] Anacetrapib potently blocks CE and TG transfer in 95% human serum.^[2]
• In Vivo: In a dyslipidemic hamster model, 60 mg/kg/day Anacetrapib for 2 weeks results in a 94% reduction in CETP activity and 47% increase in HDL-cholesterol compared with control animals; non-HDL-cholesterol concentrations are not affected. In addition, Anacetrapib promotes reverse cholesterol transport from macrophages, and leads to a 30% increase in fecal cholesterol content. HDL from Anacetrapib-treated hamsters reveals an increase in SR-B1- and ABCG1-mediated efflux compared with controls. ^[2] After oral administration of [^14C]Anacetrapib at 10 mg/kg, ～80 and 90% of the radioactive dose is recovered over 48 hous postdose from rats and monkeys, respectively. The majority of the administered radioactive dose is excreted unchanged in feces in both species. ^[3]
• Clinical Trials: Anacetrapib is in a phase III study among people with established vascular disease.

Protocol

• Protocol: Kinase Assay ^[2]
• Radioactive assays: The ability of Anacetrapib to block CETP-mediated CE and TG transfer is measured by radioactive CETP transfer assay with 2% human serum. The procedure is similar to the 95% human serum transfer assay, except that purified human HDL (128 μg/mL) and [^3H] cholesteryl oleate or [^3H] triolein-labeled LDL are used as acceptor and donor particles, respectively. The [^3H] cholesteryl oleate or [^3H] triolein from exogenous LDL to HDL is transferred by purified recombinant CETP (30 nM) in standard CETP Buffer (50 mM Tris pH 7.4, 100 nM NaCl, and 1 mM EDTA) with 2% human serum. The transfer reaction is terminated by precipitation of LDL with one volume of ice cold human serum and 2 volumes of 20% W/V PEG 8000. The samples are centrifuged and an aliquot of the HDL-containing supernatant is counted by liquid scintillation. Counts present in the supernatant for controls (without CETP addition) are subtracted from those reactivated with CETP to correct for non-specific transfer.
• Protocol: Animal Study ^[3]
• Animal Models: Adult male Sprague-Dawley rats weighing 280 to 330 g
• Formulation: In polyethylene glycol 300-water (7:3, v/v)
• Doses: 2.5 mL/kg (2.5, 25, 50, 250 mg/mL)
• Administration: Oral gavage

References

• References: [1] Niesor EJ, et al. J Lipid Res. 2010, 51(12), 3443-3454.
• References: [2] Ranalletta M, et al. J Lipid Res. 2010, 51(9), 2739-2752.
• References: [3] Tan EY, et al. Drug Metab Dispos. 2010, 38(3), 459-473.

REFERENCES

• Niesor EJ, et al. J Lipid Res. 2010, 51(12), 3443-3454.
• Ranalletta M, et al. J Lipid Res. 2010, 51(9), 2739-2752.
• Tan EY, et al. Drug Metab Dispos. 2010, 38(3), 459-473.