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Handbook chapter surveys emerging HDL-targeted drugs, from CETP inhibitors to PPAR and LXR agonists (Handb Exp Pharmacol 2015)

Original title: Emerging small molecule drugs

Handb Exp Pharmacol · · 4

Colin S, Chinetti-Gbaguidi G, Kuivenhoven JA, Staels B

Statins reduce cardiovascular risk by lowering LDL cholesterol, but substantial residual risk persists, especially in type 2 diabetes, motivating interest in raising HDL cholesterol or improving HDL function as complementary therapy given the inverse epidemiological association between HDL-C and cardiovascular risk. This chapter surveys small molecules in clinical development to pharmacologically modulate HDL-C and its functionality, including new CETP inhibitors anacetrapib and evacetrapib, novel PPAR agonists (K-877, CER-002, DSP-8658, INT131, GFT505), LXR agonists (ATI-111, LXR-623, XL-652), and RVX-208, while noting that most prior HDL-targeted therapies have failed in clinical trials due to side effects or lack of clinical benefit.

Read the paper (DOI)PubMed

Original abstract

Dyslipidaemia is a major risk factor for cardiovascular diseases. Pharmacological lowering of LDL-C levels using statins reduces cardiovascular risk. However, a substantial residual risk persists especially in patients with type 2 diabetes mellitus. Because of the inverse association observed in epidemiological studies of HDL-C with the risk for cardiovascular diseases, novel therapeutic strategies to raise HDL-C levels or improve HDL functionality are developed as complementary therapy for cardiovascular diseases. However, until now most therapies targeting HDL-C levels failed in clinical trials because of side effects or absence of clinical benefits. This chapter will highlight the emerging small molecules currently developed and tested in clinical trials to pharmacologically modulate HDL-C and functionality including new CETP inhibitors (anacetrapib, evacetrapib), novel PPAR agonists (K-877, CER-002, DSP-8658, INT131 and GFT505), LXR agonists (ATI-111, LXR-623, XL-652) and RVX-208.

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