Cholesteryl ester transfer protein inhibitors as high-density lipoprotein raising agents.
BACKGROUND
Not only hypercholesterolemia, but also low levels of high-density lipoprotein cholesterol is a critical risk factor for atherosclerosis-related disease. Therefore, there has been great interest in identifying effective and selective cholesteryl ester transfer protein (CETP) inhibitors that can raise high-density lipoprotein. Recently, Phase III clinical studies of torcetrapib, one of the CETP inhibitors developed by researchers at Pfizer, were unexpectedly terminated because of an increase in cardiovascular events and mortality. Torcetrapib has some compound-specific and off-target effects, such as raising blood pressure and aldosterone, which could affect an increase in cardiovascular events and mortality.


OBJECTIVE
The aim of this review is to provide an update (from 2000 to early 2009) on the patenting activity in the field of CETP inhibitors and the status of the most advanced compounds.


CONCLUSIONS
Dalcetrapib (JTT-705) and anacetrapib, which have not been reported to have the off-target effects of torcetrapib, are currently in Phase III. They are expected to reveal whether CETP inhibition is beneficial for atherosclerosis-related diseases.
Shinkai
Hisashi
H
Central Pharmaceutical Research Institute, JT, Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan. hisashi.shinkai@jt.com
D000577:Amides; D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000187:drug effects; D017326:Clinical Trials, Phase III as Topic; D004952:Esters; D006801:Humans; D023303:Oxazolidinones / Q000009:adverse effects / Q000494:pharmacology; D010330:Patents as Topic; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology
D000577:Amides; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004952:Esters; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C483909:torcetrapib; C530884:anacetrapib