Target Information

Target General Infomation
Target ID
T15334
Former ID
TTDC00124
Target Name
Cholesteryl ester transfer protein
Gene Name
CETP
Synonyms
Cholesterol ester transfer protein; Lipid transfer protein I; CETP
Target Type
Clinical Trial
Disease Arteriosclerosis [ICD9: 440; ICD10: I70]
Atherosclerosis [ICD9: 414.0, 440; ICD10: I70]
Cardiovascular disorder [ICD10: I00-I99]
Dyslipidaemias; Hyperlipidaemia [ICD9:272, 272.0-272.4; ICD10: E78]
Dyslipidaemias [ICD9: 272; ICD10: E78]
Hyperlipidaemia [ICD9: 272.0-272.4; ICD10: E78]
Lipid metabolism disorder [ICD10: E75-E78]
Peripheral vascular disease; Hyperlipidemia [ICD9: 272.0-272.4, 325, 430-459, 443.9; ICD10: E78, G45-G46, I60-I95, I73.9]
Function
Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL (PubMed:3600759, PubMed:24293641). Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination (PubMed:17237796).
BioChemical Class
Bactericidal permeability increasing protein
Target Validation
T15334
UniProt ID
P11597
Sequence
MLAATVLTLALLGNAHACSKGTSHEAGIVCRITKPALLVLNHETAKVIQTAFQRASYPDI
TGEKAMMLLGQVKYGLHNIQISHLSIASSQVELVEAKSIDVSIQNVSVVFKGTLKYGYTT
AWWLGIDQSIDFEIDSAIDLQINTQLTCDSGRVRTDAPDCYLSFHKLLLHLQGEREPGWI
KQLFTNFISFTLKLVLKGQICKEINVISNIMADFVQTRAASILSDGDIGVDISLTGDPVI
TASYLESHHKGHFIYKNVSEDLPLPTFSPTLLGDSRMLYFWFSERVFHSLAKVAFQDGRL
MLSLMGDEFKAVLETWGFNTNQEIFQEVVGGFPSQAQVTVHCLKMPKISCQNKGVVVNSS
VMVKFLFPRPDQQHSVAYTFEEDIVTTVQASYSKKKLFLSLLDFQITPKTVSNLTESSSE
SVQSFLQSMITAVGIPEVMSRLEVVFTALMNSKGVSLFDIINPEIITRDGFLLLQMDFGF
PEHLLVDFLQSLS
Drugs and Mode of Action
Drug(s) Anacetrapib Drug Info Phase 3 Atherosclerosis [1], [2]
Dalcetrapib Drug Info Phase 3 Dyslipidaemias; Hyperlipidaemia [3]
Evacetrapib Drug Info Phase 3 Cardiovascular disorder [4], [5]
Anacetrapib Drug Info Phase 2 Hyperlipidaemia [1], [2]
DRL-17822 Drug Info Phase 2 Arteriosclerosis [6]
JTT-302 Drug Info Phase 2 Lipid metabolism disorder [7]
TA-8995 Drug Info Phase 2 Hyperlipidaemia [8]
BAY-60-5521 Drug Info Phase 1 Arteriosclerosis [9]
BAY-38-1315 Drug Info Preclinical Arteriosclerosis [10]
CETi-1 Drug Info Discontinued in Phase 2 Arteriosclerosis [11]
Torcetrapib Drug Info Discontinued in Phase 2 Peripheral vascular disease; Hyperlipidemia [12]
CP-800569 Drug Info Discontinued in Phase 1 Atherosclerosis [13]
DS-1442 Drug Info Discontinued in Phase 1 Dyslipidaemias [14]
PF-3185043 Drug Info Discontinued in Phase 1 Atherosclerosis [15]
R7232 Drug Info Discontinued in Phase 1 Dyslipidaemias [16]
Inhibitor Anacetrapib Drug Info [17], [18], [19]
BAY-38-1315 Drug Info [20]
BAY-60-5521 Drug Info [21]
CP-800569 Drug Info [22], [23]
Dalcetrapib Drug Info [24]
DRL-17822 Drug Info [25]
Evacetrapib Drug Info [25]
JTT-302 Drug Info [25]
NSC-40331 Drug Info [26]
NSC-89508 Drug Info [26]
PF-3185043 Drug Info [22], [23]
R7232 Drug Info [27], [24]
SC-795 Drug Info [26]
TA-8995 Drug Info [28]
TETRAHYDROQUINOLINE A Drug Info [29]
TETRAHYDROQUINOLINE B Drug Info [29]
Torcetrapib Drug Info [17], [30], [31]
Modulator DS-1442 Drug Info [32]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
PANTHER Pathway CCKR signaling map ST
Reactome LDL-mediated lipid transport
HDL-mediated lipid transport
WikiPathways Statin Pathway
Lipid digestion, mobilization, and transport
References
REF 1Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8400).
REF 3ClinicalTrials.gov (NCT00658515) A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome. U.S. National Institutes of Health.
REF 4ClinicalTrials.gov (NCT02227784) A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol. U.S. National Institutes of Health.
REF 5(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8401).
REF 6ClinicalTrials.gov (NCT01388816) A Safety and Efficacy Study of DRL-17822, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Patients With Abnormal Cholesterol Levels. U.S. National Institutes of Health.
REF 7ClinicalTrials.gov (NCT00748852) Safety Study of JTT-302 in Subjects With Low HDL-C Levels. U.S. National Institutes of Health.
REF 8ClinicalTrials.gov (NCT01970215) TA-8995: Its Use in Patients With Mild Dyslipidaemia (TULIP). U.S. National Institutes of Health.
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034993)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017234)
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008445)
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015157)
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025536)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036983)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025537)
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027351)
REF 17The end of the road for CETP inhibitors after torcetrapib? Curr Opin Cardiol. 2009 Jul;24(4):364-71.
REF 18Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Apr;31(3):183-227.
REF 19Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Br J Clin Pharmacol. 2009 May;67(5):520-6. Epub 2009 Feb 4.
REF 20Chromanol derivatives--a novel class of CETP inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):488-91.
REF 21Single dose pharmacokinetics, pharmacodynamics, tolerability and safety of BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein. Br J Clin Pharmacol. 2012 Feb;73(2):210-8.
REF 22Pfizer. Product Development Pipeline. March 31 2009.
REF 23Flavonoids as inhibitors of MRP1-like efflux activity in human erythrocytes. A structure-activity relationship study. Oncol Res. 2003;13(11):463-9.
REF 24Clinical pipeline report, company report or official report of Roche (2009).
REF 25The dyslipidaemia market. Nat Rev Drug Discov. 2014 Nov;13(11):807-8.
REF 26Eur 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 27Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. J Neurooncol. 2015 Feb;121(3):557-63.
REF 28Amgen To Acquire Privately-Held Dezima Pharma
REF 29Bioorg 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 30A Translational Medicine perspective of the development of torcetrapib: Does the failure of torcetrapib development cast a shadow on future development of lipid modifying agents, HDL elevation strategies or CETP as a viable molecular target for atherosclerosis? A case study of the use of biomarkers and Translational Medicine in atherosclerosis drug discovery and development. Biochem Pharmacol. 2009 Aug 15;78(4):315-25. Epub 2009 Mar 24.
REF 31Safety and tolerability of dalcetrapib. Am J Cardiol. 2009 Jul 1;104(1):82-91.
REF 32Ds-1442b is a Novel, Potent Cetp Inhibitor That Reduces Atherosclerosis by Hdl Elevation and Non-hdl Reduction. Circulation. 2012; 126: A11806.

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