Anacetrapib (MK-0859)

2 years -80 in solvent

Oral gavage

Anacetrapib is in a phase III study among people with established vascular disease.

In polyethylene glycol 300-water (7:3, v/v)

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-beta-HDL formation by more than 46%. [1] Anacetrapib potently blocks CE and TG transfer in 95% human serum.[2]

[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 ug/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.

Anacetrapib (MK0859) is a potent, selective, reversible rhCETP and mutant CETP(C13S) inhibitor with IC50 of 7.9 nM and 11.8 nM, increases HDL-C and decreases LDL-C, does not increase aldosterone or blood pressure. Phase 3.