REVIEW
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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.

CONCLUSION: 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.

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