Raising high-density lipoprotein with cholesteryl ester transfer protein inhibitors.
Cholesteryl ester transfer protein (CETP) catalyzes the transfer of cholesteryl ester from high-density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins in exchange for triglyceride, and thereby plays a major role in lipoprotein metabolism. The reciprocal increase in HDL cholesterol (HDL-C) and decrease in low-density lipoprotein cholesterol (LDL-C) associated with CETP deficiency has led to the search for synthetic CETP inhibitors over the past 15 years. Several potent inhibitors have been identified, two of which--JTT-705 and torcetrapib--are undergoing clinical trials. Recent reports that torcetrapib is able to simultaneously raise HDL-C twofold and lower LDL-C by < or = 42% has heightened interest in this new class of agents. Upcoming results from Phase III trials of torcetrapib should provide anatomical measurements of atherosclerosis and thus the first assessment of therapeutic benefit.
Clark
Ronald W
RW
Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA. Ronald.W.Clark@pfizer.com
D000577:Amides; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D002352:Carrier Proteins / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000502:physiology; D053480:Cholesterol Ester Transfer Proteins; D002986:Clinical Trials as Topic; D004952:Esters; D005260:Female; D006023:Glycoproteins / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D011804:Quinolines / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*
D000577:Amides; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D011804:Quinolines; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C483909:torcetrapib