Division of Translational Medicine and Human Genetics, Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, and.
Annu Rev Med. 2014;65:385-403. doi: 10.1146/annurev-med-050311-163305.
The cholesteryl ester transfer protein (CETP) plays an integral role in the metabolism of plasma lipoproteins. Despite two failures, CETP inhibitors are still in clinical development. We review the genetics of CETP and coronary disease, preclinical data on CETP inhibition and atherosclerosis, and the effects of CETP inhibition on cholesterol efflux and reverse cholesterol transport. We discuss the two failed CETP inhibitors, torcetrapib and dalcetrapib, and attempt to extract lessons learned. Two CETP inhibitors, anacetrapib and evacetrapib, are in phase III development, and we attempt to differentiate them from the failed drugs. Whether pharmacologic CETP inhibition will reduce the risk of cardiovascular disease is one of the most fascinating and important questions in the field of cardiovascular medicine.
胆固醇酯转移蛋白（CETP）在血浆脂蛋白代谢中发挥着重要作用。尽管有两次失败，CETP 抑制剂仍在临床开发中。我们回顾了 CETP 与冠心病的遗传学、CETP 抑制与动脉粥样硬化的临床前数据，以及 CETP 抑制对胆固醇流出和胆固醇逆向转运的影响。我们讨论了两种失败的 CETP 抑制剂，torcetrapib 和 dalcetrapib，并试图从中吸取教训。两种 CETP 抑制剂，anacetrapib 和 evacetrapib，正在进行 III 期临床试验，我们试图将它们与失败的药物区分开来。CETP 抑制是否能降低心血管疾病的风险，是心血管医学领域最引人关注和最重要的问题之一。
