Torcetrapib
A review argues ABCA1 and ABCG1 transporters, not raw HDL cholesterol level, drive HDL's atheroprotective effect after the torcetrapib failure (Cell Metab 2008)
Original title: HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis
This review examines HDL as a target for atherosclerosis treatment in light of the failure of torcetrapib, a CETP inhibitor that markedly raised HDL levels in clinical trial but called the efficacy of HDL elevation into doubt. The authors note that recent analysis suggests the failure of torcetrapib may have stemmed from off-target toxicity rather than the CETP-inhibition mechanism itself, and that HDL remains functional and promotes atherosclerosis regression. New studies highlighted in the review point to the central importance of the ATP-binding cassette transporters ABCA1 and ABCG1 in reducing macrophage foam cell formation, inflammation, and atherosclerosis, suggesting that a variety of approaches to raising HDL may eventually succeed in treating atherosclerosis where torcetrapib did not.
Original abstract
High-density lipoprotein (HDL) has been identified as a potential target in the treatment of atherosclerotic vascular disease. The failure of torcetrapib, an inhibitor of cholesteryl ester transfer protein (CETP) that markedly increased HDL levels in a clinical trial, has called into doubt the efficacy of HDL elevation. Recent analysis suggests that failure may have been caused by off-target toxicity and that HDL is functional and promotes regression of atherosclerosis. New studies highlight the central importance of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 in reducing macrophage foam cell formation, inflammation, and atherosclerosis. A variety of approaches to increasing HDL may eventually be successful in treating atherosclerosis.
HDL biologymechanismstorcetrapib
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.