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Anacetrapib

Catalog No. S2748 Name Selleck Chemicals
CAS Number 875446-37-0 Website http://www.selleckchem.com
M. F. C30H25F10NO3 Telephone (877) 796-6397
M. W. 637.508432 Fax (832) 582-8590
Purity Email sales@selleckchem.com
Storage -20°C Chembase ID: 73301

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