Update on the discovery and development of cholesteryl ester transfer protein inhibitors for reducing residual cardiovascular risk.
Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester and triglycerides between plasma lipoprotein particles HDL and LDL/VLDL, resulting in equilibration between these lipoprotein fractions. Therapy that modulates HDL metabolism to increase HDL-c levels could be an effective strategy to reduce residual cardiovascular risk since it is estimated that for each mg/dL increase in plasma HDL cholesterol, there could be a 2-3% decrease in cardiovascular risk. Modification of the lipoprotein profile by CETP inhibitors is promising, but the beneficial effect of reducing coronary heart disease risk has not yet been proven. To date, four CETP inhibitors have advanced to phase 3 cardiovascular outcome clinical trials, and two have been terminated for off-target adverse effects and lack of efficacy. This perspective will summarize recent events, new research developments, and the discovery of new classes of CETP inhibitors.
Lilly Research Laboratories, Eli Lilly and Co. , Indianapolis, Indiana 46285, United States.
Nathan B
NB
Mantlo
Ana
A
Escribano
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D055808:Drug Discovery; D006801:Humans; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000627:therapeutic use; D012307:Risk Factors; D013329:Structure-Activity Relationship
D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D023303:Oxazolidinones; D001569:Benzodiazepines; C568301:evacetrapib; C530884:anacetrapib