Sandbox 215: Difference between revisions
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The pharmaceutical industry tries to develop inhibitors of CETP in order to decrease the risk of cardivascular diseases. The goal of these inhibitors is to increase the concentration of HDL and decrease the concentration of LDL by blocking cholesteryl esters and triglyceride tranfer. Several inhibitors were found: the first is Torcetrapib followed of Anacetrapib, Dalcetrapib and Evacetrapib. | The pharmaceutical industry tries to develop inhibitors of CETP in order to decrease the risk of cardivascular diseases. The goal of these inhibitors is to increase the concentration of HDL and decrease the concentration of LDL by blocking cholesteryl esters and triglyceride tranfer. Several inhibitors were found: the first is Torcetrapib followed of Anacetrapib, Dalcetrapib and Evacetrapib. | ||
Torcetrapib was developed by Pfizer in order to treat hypercholesterolemia (high cholesterol levels) and prevent [http://en.wikipedia.org/wiki/Atherosclerosis atherosclerosis]. Torcetrapib managed to reduce CETP activity and succeeds in increasing the level of HDL. However, at the stage-III of the clinical trial, Torcetrapib causes significant changes in vital signs: like increases the blood pressure, the concentration of sodium, bicarbonate and aldosterone. | Torcetrapib was developed by Pfizer in order to treat hypercholesterolemia (high cholesterol levels) and prevent [http://en.wikipedia.org/wiki/Atherosclerosis atherosclerosis]. Torcetrapib managed to reduce CETP activity and succeeds in increasing the level of HDL. However, at the stage-III of the clinical trial, Torcetrapib causes significant changes in vital signs: like increases the blood pressure, the concentration of sodium, bicarbonate and aldosterone. The explanations for this unexpected result remain unclear. Maybe increased binding of torcetrapib-CETP complexes to HDL interferes with some of the anti-cardiovascular diseases (anti-CVD) activity of HDL causing the death of many persons. That's why, in 2006, this inhibitor was halted. | ||
Unlike to Torcetrapib, the other which still are in clinical trial do not | Unlike to Torcetrapib, the other which still are in clinical trial do not have any side effects. | ||
Evacetrapib | Evacetrapib is deseems to give the more promising results. Evacetrapib increases the level of HDL without elevates blood pressure or aldosterone <ref>Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. The Journal of Lipid Research, December 2011. [https://www-ncbi-nlm-nih-gov.scd-rproxy.u-strasbg.fr/pubmed/21957197 PMID: 21957197]. [http://www.jlr.org.scd-rproxy.u-strasbg.fr/content/52/12/2169.long doi: 10.1194/jlr.M018069]</ref> | ||
The molecular explanations for | |||
this unexpected result are not clear | |||
Perhaps | |||
increased binding of torcetrapib–CETP | |||
complexes to HDL interferes with some of | |||
the anti-CVD activity of HDL, such as its | |||
anti-inflammatory or antioxidant properties17. | |||
==External ressources== | ==External ressources== | ||
