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[摘要]：Low levels of high-density lipoprotein cholesterol (HDL-C) constitute a major independent cardiovascular risk factor. Novel strategies for raising HDL-C to address residual cardiovascular risk after statin treatment are required. Cholesteryl ester transfer protein (CETP) inhibitors are small molecules that interact with CETP and inhibit its capacity to facilitate heteroexchange of neutral lipids (cholesteryl esters and triglycerides) between HDL and apolipoprotein B (Apo B)-containing lipoproteins. CETP inhibitors are presently the most potent HDL-raising agents, with a dose-dependent HDL-C elevation of up to +150%. Based on these findings, three small-molecule inhibitors of CETP torcetrapib, dalcetrapib (JTT-705) and anacetrapib (MK-0859), have been developed, which induce increases in circulating concentrations of HDL-C while decreasing those of low-density lipoprotein cholesterol (LDL-C) and Apo B. While the development of torcetrapib was abandoned as a result of excessive mortality in clinical trials, potentially reflecting its hypertensive effect related to elevated aldosterone levels, anacetrapib holds promise as the only drug belonging to this class that combines high potency with a good safety profile. |
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