Target Validation Information
Target ID T15334
Target Name Cholesteryl ester transfer protein
Target Type
Clinical Trial
Drug Potency against Target SC-795 Drug Info IC50 = 20 nM [530670]
Dalcetrapib Drug Info IC50 = 6 nM [552951]
NSC-40331 Drug Info IC50 = 6500 nM [530670]
TETRAHYDROQUINOLINE A Drug Info IC50 = 39 nM [530053]
Anacetrapib Drug Info IC50 = 16 nM [552951]
NSC-89508 Drug Info IC50 = 1900 nM [530670]
Torcetrapib Drug Info IC50 = 50 nM [552951]
Action against Disease Model Dalcetrapib The mechanism by which cholesteryl ester transfer protein (CETP) activity affects HDL metabolism was investigated using agents that selectively target CETP (dalcetrapib, torcetrapib, anacetrapib). In contrast with torcetrapib and anacetrapib, dalcetrapib requires cysteine 13 to decrease CETP activity, measured as transfer of cholesteryl ester (CE) from HDL to LDL, and does not affect transfer of CE from HDL3 to HDL2. Only dalcetrapib induced a conformational change in CETP, when added to h uMan plasma in vitro, also observed in vivo and correlated with CETP activity. CETP-induced pre-beta-HDL formation in vitro in h uMan plasma was unchanged by dalcetrapib ??? |?M and increased at 10 |?M. [553070] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the exchange of neutral lipids among the lipoprotein. Because the principal core lipid of very-low-density lipoprotein (VLDL) is triglyceride and that of high-density lipoprotein (HDL) is cholesterol ester, CETP mediates a 'heteroexchange' of cholesterol ester for triglyceride between those lipoproteins. As a result, animals that express CETP tend to have higher VLDL and low-density lipoprotein (LDL) cholesterol levels, whereas those with no CETP activity tend to have high HDL cholesterol levels.Because VLDL and LDL are associated with the progression of atherosclerosis, and HDL are considered anti-atherogenic, CETP could be an 'atherogenic' protein, that is, given the other conditions required for atherosclerosis to develop, expression of CETP would accelerate the rate at which the arterial lesions progress. We report here that transgenic mice expressing CETP had much worse atherosclerosis than did non-expressing controls, and we suggest that the increase in lesion severity was due largely to CETP-induced alterations in the lipoprotein profile [530670]
References
Ref 530670Eur J Med Chem. 2010 Apr;45(4):1598-617. Epub 2010 Jan 14.Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration.
Ref 552951Cholesteryl ester transfer protein (CETP) inhibitors. Curr Top Med Chem. 2009;9(5):419-27.
Ref 530670Eur J Med Chem. 2010 Apr;45(4):1598-617. Epub 2010 Jan 14.Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration.
Ref 530053Bioorg Med Chem Lett. 2009 May 1;19(9):2456-60. Epub 2009 Mar 18.Design and synthesis of potent inhibitors of cholesteryl ester transfer protein (CETP) exploiting a 1,2,3,4-tetrahydroquinoline platform.
Ref 552951Cholesteryl ester transfer protein (CETP) inhibitors. Curr Top Med Chem. 2009;9(5):419-27.
Ref 530670Eur J Med Chem. 2010 Apr;45(4):1598-617. Epub 2010 Jan 14.Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration.
Ref 553070Modulating cholesteryl ester transfer protein activity maintains efficient pre--HDL formation and increases reverse cholesterol transport. J Lipid Res. 2010 Dec;51(12):3443-54. doi: 10.1194/jlr.M008706. Epub 2010 Sep 22.
Ref 552951Cholesteryl ester transfer protein (CETP) inhibitors. Curr Top Med Chem. 2009;9(5):419-27.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.