CETP inhibitor

From Wikipedia, the free encyclopedia
Jump to: navigation, search

A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP).[1][2][3][4]They are intended to reduce the risk of atherosclerosis (a cardiovascular disease) by improving blood lipid levels. This category of drugs substantially increases HDL and reverse cholesterol transport. As of December, 2012, these drugs have generally failed in trials, either causing a marked increase in deaths (Torcetrapib), or having no meaningful clinical improvement despite HDL increases (Dalcetrapib).

In testing:

  • Anacetrapib, encouraging phase IIb interim results in 2010. Two phase III trials are running until 2017.
  • Evacetrapib, phase II study results published in November 2011.[5] Phase III trails will run though 2016.

Failed:

  • Torcetrapib, failed in 2006 - excess deaths in phase III.
  • Dalcetrapib, development halted in May 2012 when Phase III trials failed to show clinically meaningful efficacy. [6]

Mechanism[edit]

CETP inhibitors inhibit cholesterylester transfer protein (CETP), which normally transfers cholesterol from HDL cholesterol to very low density or low density lipoproteins (VLDL or LDL). Inhibition of this process results in higher HDL levels (the "good" cholesterol-containing particle) and reduces LDL levels (the "bad" cholesterol).[citation needed]

References[edit]

  1. ^ Tall AR (March 2007). "CETP inhibitors to increase HDL cholesterol levels". N. Engl. J. Med. 356 (13): 1364–6. doi:10.1056/NEJMe078029. PMID 17387130. 
  2. ^ Joy TR, Hegele RA (August 2008). "The failure of torcetrapib: what have we learned?". Br. J. Pharmacol. 154 (7): 1379–81. doi:10.1038/bjp.2008.248. PMC 2492099. PMID 18536741. 
  3. ^ Rennings AJ, Stalenhoef AF (October 2008). "JTT-705: is there still future for a CETP inhibitor after torcetrapib?". Expert Opin Investig Drugs 17 (10): 1589–97. doi:10.1517/13543784.17.10.1589. PMID 18808319. 
  4. ^ Carmen Drahl (February 2012). "The Cholesterol Bet". Chemical & Engineering News 90 (8): 13–20. 
  5. ^ Stephen J. Nicholls et al. (2011). "Effects of the CETP Inhibitor Evacetrapib Administered as Monotherapy or in Combination With Statins on HDL and LDL Cholesterol: A Randomized Controlled Trial". JAMA 306 (19): 2099–2109. doi:10.1001/jama.2011.1649. 
  6. ^ Larry Husten (May 2012). "Roche Terminates Development Of CETP Inhibitor Dalcetrapib". Forbes.