The discovery of new cholesteryl ester transfer protein inhibitors.
Cholesteryl ester transfer protein (CETP) has been an important but controversial target for elevating HDLc (high density lipoprotein cholesterol) and treating atherosclerosis. Significant progress toward inhibiting CETP has occurred on several fronts, including the development of an antisense inhibitor, irreversible small molecule inhibitors and reversible small molecule inhibitors. Several orally bioavailable, small molecule CETP inhibitors have shown potential to improve the HDLc to LDLc (low density lipoprotein cholesterol) ratio in various animal models at reasonable doses, and one of these compounds has shown efficacy in preventing atherosclerosis in a rabbit model. However, several more years of clinical testing will likely be needed to demonstrate that these clinical candidates can provide a potential therapeutic benefit to patients with coronary artery disease.
Sikorski
J A
JA
Discovery Research, Medicinal Chemistry, AtheroGenics Inc., 8995 Westside Parkway, Alpharetta, GA 30004, USA. jsikorski@atherogenics.com
Connolly
D T
DT
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D006801:Humans; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000924:Anticholesteremic Agents; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008074:Lipoproteins; D016376:Oligonucleotides, Antisense; D010455:Peptides