Target Information
| Target General Information | Top | |||||
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| Target ID |
T15334
(Former ID: TTDC00124)
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| Target Name |
Cholesteryl ester transfer protein (CETP)
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| Synonyms |
Lipid transfer protein I; Cholesterol ester transfer protein
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| Gene Name |
CETP
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Arterial occlusive disease [ICD-11: BD40] | |||||
| 2 | Cardiovascular disease [ICD-11: BA00-BE2Z] | |||||
| 3 | Hyper-lipoproteinaemia [ICD-11: 5C80] | |||||
| 4 | Myocardial infarction [ICD-11: BA41-BA43] | |||||
| Function |
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. Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination. Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles.
Click to Show/Hide
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| BioChemical Class |
Bactericidal permeability increasing protein
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| UniProt ID | ||||||
| Sequence |
MLAATVLTLALLGNAHACSKGTSHEAGIVCRITKPALLVLNHETAKVIQTAFQRASYPDI
TGEKAMMLLGQVKYGLHNIQISHLSIASSQVELVEAKSIDVSIQNVSVVFKGTLKYGYTT AWWLGIDQSIDFEIDSAIDLQINTQLTCDSGRVRTDAPDCYLSFHKLLLHLQGEREPGWI KQLFTNFISFTLKLVLKGQICKEINVISNIMADFVQTRAASILSDGDIGVDISLTGDPVI TASYLESHHKGHFIYKNVSEDLPLPTFSPTLLGDSRMLYFWFSERVFHSLAKVAFQDGRL MLSLMGDEFKAVLETWGFNTNQEIFQEVVGGFPSQAQVTVHCLKMPKISCQNKGVVVNSS VMVKFLFPRPDQQHSVAYTFEEDIVTTVQASYSKKKLFLSLLDFQITPKTVSNLTESSSE SVQSFLQSMITAVGIPEVMSRLEVVFTALMNSKGVSLFDIINPEIITRDGFLLLQMDFGF PEHLLVDFLQSLS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T48UT8 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | Anacetrapib | Drug Info | Phase 3 | Arteriosclerosis | [2], [3] | |
| 2 | Dalcetrapib | Drug Info | Phase 3 | Hyperlipidaemia | [4] | |
| 3 | Evacetrapib | Drug Info | Phase 3 | Cardiovascular disease | [5], [6] | |
| 4 | DRL-17822 | Drug Info | Phase 2 | Arteriosclerosis | [7] | |
| 5 | JTT-302 | Drug Info | Phase 2 | Lipid metabolism disorder | [8] | |
| 6 | TA-8995 | Drug Info | Phase 2 | Hyperlipidaemia | [9] | |
| 7 | BAY-60-5521 | Drug Info | Phase 1 | Arteriosclerosis | [10] | |
| Discontinued Drug(s) | [+] 6 Discontinued Drugs | + | ||||
| 1 | CETi-1 | Drug Info | Discontinued in Phase 2 | Arteriosclerosis | [11] | |
| 2 | Torcetrapib | Drug Info | Discontinued in Phase 2 | Hyperlipidaemia | [12] | |
| 3 | CP-800569 | Drug Info | Discontinued in Phase 1 | Arteriosclerosis | [13] | |
| 4 | DS-1442 | Drug Info | Discontinued in Phase 1 | Dyslipidemia | [14] | |
| 5 | PF-3185043 | Drug Info | Discontinued in Phase 1 | Arteriosclerosis | [15] | |
| 6 | R7232 | Drug Info | Discontinued in Phase 1 | Dyslipidemia | [16] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | BAY-38-1315 | Drug Info | Preclinical | Arteriosclerosis | [17] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 17 Inhibitor drugs | + | ||||
| 1 | Anacetrapib | Drug Info | [18], [19], [20] | |||
| 2 | Dalcetrapib | Drug Info | [1] | |||
| 3 | Evacetrapib | Drug Info | [21] | |||
| 4 | DRL-17822 | Drug Info | [21] | |||
| 5 | JTT-302 | Drug Info | [21] | |||
| 6 | TA-8995 | Drug Info | [22] | |||
| 7 | BAY-60-5521 | Drug Info | [23] | |||
| 8 | Torcetrapib | Drug Info | [20], [25], [26] | |||
| 9 | CP-800569 | Drug Info | [27], [28] | |||
| 10 | PF-3185043 | Drug Info | [27], [28] | |||
| 11 | R7232 | Drug Info | [1], [30] | |||
| 12 | BAY-38-1315 | Drug Info | [31] | |||
| 13 | NSC-40331 | Drug Info | [32] | |||
| 14 | NSC-89508 | Drug Info | [32] | |||
| 15 | SC-795 | Drug Info | [32] | |||
| 16 | TETRAHYDROQUINOLINE A | Drug Info | [33] | |||
| 17 | TETRAHYDROQUINOLINE B | Drug Info | [33] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | DS-1442 | Drug Info | [29] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | CCKR signaling map ST | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | LDL-mediated lipid transport | |||||
| 2 | HDL-mediated lipid transport | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Statin Pathway | |||||
| 2 | Lipid digestion, mobilization, and transport | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of Roche (2009). | |||||
| REF 2 | URL: 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 3 | Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81. | |||||
| REF 4 | ClinicalTrials.gov (NCT00658515) A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome. U.S. National Institutes of Health. | |||||
| REF 5 | URL: 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 6 | ClinicalTrials.gov (NCT02227784) A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.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 8 | ClinicalTrials.gov (NCT00748852) Safety Study of JTT-302 in Subjects With Low HDL-C Levels. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT01970215) TA-8995: Its Use in Patients With Mild Dyslipidaemia (TULIP). U.S. National Institutes of Health. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034993) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008445) | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015157) | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025536) | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036983) | |||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025537) | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027351) | |||||
| REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017234) | |||||
| REF 18 | Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (C... Br J Clin Pharmacol. 2009 May;67(5):520-6. | |||||
| REF 19 | Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Apr;31(3):183-227. | |||||
| REF 20 | The end of the road for CETP inhibitors after torcetrapib Curr Opin Cardiol. 2009 Jul;24(4):364-71. | |||||
| REF 21 | The dyslipidaemia market. Nat Rev Drug Discov. 2014 Nov;13(11):807-8. | |||||
| REF 22 | Amgen To Acquire Privately-Held Dezima Pharma | |||||
| REF 23 | Single 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 24 | CETi-1. AVANT. Curr Opin Investig Drugs. 2004 Mar;5(3):334-8. | |||||
| REF 25 | Safety and tolerability of dalcetrapib. Am J Cardiol. 2009 Jul 1;104(1):82-91. | |||||
| REF 26 | A Translational Medicine perspective of the development of torcetrapib: Does the failure of torcetrapib development cast a shadow on future develop... Biochem Pharmacol. 2009 Aug 15;78(4):315-25. | |||||
| REF 27 | Pfizer. Product Development Pipeline. March 31 2009. | |||||
| REF 28 | Flavonoids as inhibitors of MRP1-like efflux activity in human erythrocytes. A structure-activity relationship study. Oncol Res. 2003;13(11):463-9. | |||||
| REF 29 | Ds-1442b is a Novel, Potent Cetp Inhibitor That Reduces Atherosclerosis by Hdl Elevation and Non-hdl Reduction. Circulation. 2012; 126: A11806. | |||||
| REF 30 | Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. J Neurooncol. 2015 Feb;121(3):557-63. | |||||
| REF 31 | Chromanol derivatives--a novel class of CETP inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):488-91. | |||||
| REF 32 | Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic expl... Eur J Med Chem. 2010 Apr;45(4):1598-617. | |||||
| REF 33 | Design and synthesis of potent inhibitors of cholesteryl ester transfer protein (CETP) exploiting a 1,2,3,4-tetrahydroquinoline platform. Bioorg Med Chem Lett. 2009 May 1;19(9):2456-60. | |||||
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