CETP and its inhibitors, a foundational review: structure, mechanism, non-lipid functions and the full outcomes-trial record for four small-molecule inhibitors (J Lipid Res 2018)

Original title: Cholesteryl ester transfer protein and its inhibitors

J Lipid Res · 27 February 2018 · 6

Shrestha S, Wu BJ, Guiney L, Barter PJ, Rye KA

A comprehensive review of CETP, which mediates bidirectional transfer of cholesteryl esters and triglycerides between plasma lipoproteins, moving cholesteryl ester from HDL to VLDL and LDL while moving triglyceride from VLDL to LDL and HDL. Because inhibiting CETP raises HDL cholesterol while lowering VLDL and LDL cholesterol, it has long been considered a candidate approach for reducing atherosclerotic cardiovascular disease, motivating development of neutralising monoclonal antibodies, vaccines, antisense oligonucleotides and small-molecule inhibitors. The review covers the structure and mechanism of action of CETP, its regulation, and its non-lipid-transporting functions, then summarises the results of the large-scale cardiovascular outcomes trials for the four small-molecule CETP inhibitors that reached that stage, providing a foundational reference for the field.

Original abstract

Most of the cholesterol in plasma is in an esterified form that is generated in potentially cardioprotective HDLs. Cholesteryl ester transfer protein (CETP) mediates bidirectional transfers of cholesteryl esters (CEs) and triglycerides (TGs) between plasma lipoproteins. Because CE originates in HDLs and TG enters the plasma as a component of VLDLs, activity of CETP results in a net mass transfer of CE from HDLs to VLDLs and LDLs, and of TG from VLDLs to LDLs and HDLs. As inhibition of CETP activity increases the concentration of HDL-cholesterol and decreases the concentration of VLDL- and LDL-cholesterol, it has the potential to reduce atherosclerotic CVD. This has led to the development of anti-CETP neutralizing monoclonal antibodies, vaccines, and antisense oligonucleotides. Small molecule inhibitors of CETP have also been developed and four of them have been studied in large scale cardiovascular clinical outcome trials. This review describes the structure of CETP and its mechanism of action. Details of its regulation and nonlipid transporting functions are discussed, and the results of the large scale clinical outcome trials of small molecule CETP inhibitors are summarized.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.