Cholesteryl ester transfer protein (CETP) catalyzes the exchange of cholesteryl esters from high-density lipoprotein (HDL) cholesterol to apolipoprotein B-containing lipoproteins, including very low-density lipoprotein (VLDL) and LDL. Torcetrapib is an inhibitor of CETP activity (IC50 = 50 nM) that raises HDL cholesterol and reduces LDL cholesterol levels by forming a nonproductive complex between CETP and HDL. Although torcetrapib produced consistent antiatherogenic effects in rabbits, clinical trials of torcetrapib were terminated early due to deleterious hypertensive effects. PDGFR, HGFR (c-Met), IL-2 receptor, and ErbB1- tyrosine kinase have subsequently been identified as direct off-targets of this compound.
