Clark Ronald W
Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA.
Curr Opin Pharmacol. 2006 Apr;6(2):162-8. doi: 10.1016/j.coph.2005.10.012. Epub 2006 Feb 17.
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.
胆固醇酯转运蛋白（CETP）催化胆固醇酯从高密度脂蛋白（HDL）转移至含载脂蛋白B的脂蛋白，以交换甘油三酯，因此在脂蛋白代谢中起主要作用。过去15年里，与CETP缺乏相关的HDL胆固醇（HDL-C）升高及低密度脂蛋白胆固醇（LDL-C）降低促使人们寻找合成CETP抑制剂。已鉴定出几种强效抑制剂，其中两种——JTT-705和托彻普（torcetrapib）——正在进行临床试验。最近有报道称，托彻普能够使HDL-C同时升高两倍，并使LDL-C降低≤42%，这引发了人们对这类新型药物的更大兴趣。托彻普III期试验即将公布的结果应能提供动脉粥样硬化的解剖学测量数据，从而首次评估其治疗益处。
