Abstract

Inhibitors of cholesterol ester transfer protein (CETP) have the capacity to increase plasma high-density lipoprotein cholesterol to unprecedented levels. Still, hopes that CETP inhibition could reduce atherosclerosis were dented when the clinical development of one such inhibitor, torcetrapib, was halted because of an unexpected finding of increased cardiovascular and noncardiovascular mortality against a background of elevated blood pressure and plasma aldosterone levels. Recently, evidence has accumulated to show that these untoward effects may have been largely attributable to off-target toxicity of the compound, unrelated to the mechanism of CETP inhibition and not shared by other CETP inhibitors. In this review, we explore the rationale for CETP inhibition, compare the pharmacology of the small molecule CETP inhibitors that reached clinical development, and address the evidence relating to off-target adverse effects.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.