Anacetrapib

Anacetrapib (codenamed MK-0859) is a potent cholesteryl ester transfer protein (CETP) inhibitor being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Anacetrapib binds reversibly and dalcetrapib covalently to CETP. Anacetrapib inhibited CETP-mediated cholesteryl ester and triglyceride transfer with similar potencies. Anacetrapib potently blocks CE and TG transfer in 95% human serum. Single doses of anacetrapib markedly and dose-dependently inhibited serum CETP activity with peak effects of approximately 90% inhibition at t(max) and approximately 58% inhibition at 24 h post-dose. In addition, Anacetrapib promotes reverse cholesterol transport from macrophages, and leads to a 30% increase in fecal cholesterol content.