Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFQAYR)

• DTT Name: Cholesteryl ester transfer protein (CETP)
• Synonyms: Lipid transfer protein I; Cholesterol ester transfer protein
• Gene Name: CETP
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Bactericidal permeability increasing protein
• UniProt ID: CETP_HUMAN
• TTD ID: T15334
• Sequence:
  MLAATVLTLALLGNAHACSKGTSHEAGIVCRITKPALLVLNHETAKVIQTAFQRASYPDI
  TGEKAMMLLGQVKYGLHNIQISHLSIASSQVELVEAKSIDVSIQNVSVVFKGTLKYGYTT
  AWWLGIDQSIDFEIDSAIDLQINTQLTCDSGRVRTDAPDCYLSFHKLLLHLQGEREPGWI
  KQLFTNFISFTLKLVLKGQICKEINVISNIMADFVQTRAASILSDGDIGVDISLTGDPVI
  TASYLESHHKGHFIYKNVSEDLPLPTFSPTLLGDSRMLYFWFSERVFHSLAKVAFQDGRL
  MLSLMGDEFKAVLETWGFNTNQEIFQEVVGGFPSQAQVTVHCLKMPKISCQNKGVVVNSS
  VMVKFLFPRPDQQHSVAYTFEEDIVTTVQASYSKKKLFLSLLDFQITPKTVSNLTESSSE
  SVQSFLQSMITAVGIPEVMSRLEVVFTALMNSKGVSLFDIINPEIITRDGFLLLQMDFGF
  PEHLLVDFLQSLS
• 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.
• KEGG Pathway: Cholesterol metabolism (hsa04979)
• Reactome Pathway:
  HDL-mediated lipid transport (R-HSA-194223)
  LDL-mediated lipid transport (R-HSA-171052)

Molecular Interaction Atlas (MIA) of This DTT

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anacetrapib	DMP2BFG	Arteriosclerosis	BD40	Phase 3	[2]
Dalcetrapib	DMKNCVM	Acute coronary syndrome	BA41	Phase 3	[1]
Evacetrapib	DMCDZ15	Cardiovascular disease	BA00-BE2Z	Phase 3	[3]
DRL-17822	DMGD3XT	Arteriosclerosis	BD40	Phase 2	[3]
JTT-302	DMGLVBI	Lipid metabolism disorder	5C52.Z	Phase 2	[3]
TA-8995	DMAZHT0	Cardiovascular disease	BA00-BE2Z	Phase 2	[4]
BAY-60-5521	DMXIDWE	Arteriosclerosis	BD40	Phase 1	[5]

6 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CETi-1	DMUG5OB	Arteriosclerosis	BD40	Discontinued in Phase 2	[6]
Torcetrapib	DMDHYM7	Hyperlipidaemia	5C80	Discontinued in Phase 2	[7]
CP-800569	DMZ0YU7	Arteriosclerosis	BD40	Discontinued in Phase 1	[8]
DS-1442	DMS4IBW	Dyslipidemia	5C80-5C81	Discontinued in Phase 1	[9]
PF-3185043	DMCFYZM	Arteriosclerosis	BD40	Discontinued in Phase 1	[8]
R7232	DMETAP8	Dyslipidemia	5C80-5C81	Discontinued in Phase 1	[1]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY-38-1315	DMVESTF	Arteriosclerosis	BD40	Preclinical	[10]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NSC-40331	DMCFNMK	Discovery agent	N.A.	Investigative	[11]
NSC-89508	DMGS6HB	Discovery agent	N.A.	Investigative	[11]
SC-795	DMZN7YT	Discovery agent	N.A.	Investigative	[11]
TETRAHYDROQUINOLINE A	DMWRZJX	Discovery agent	N.A.	Investigative	[12]
TETRAHYDROQUINOLINE B	DMHT61V	Discovery agent	N.A.	Investigative	[12]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	8.86E-01	-0.1	-0.6

References

• [1] Clinical pipeline report, company report or official report of Roche (2009).
• [2] 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.
• [3] The dyslipidaemia market. Nat Rev Drug Discov. 2014 Nov;13(11):807-8.
• [4] Amgen To Acquire Privately-Held Dezima Pharma
• [5] 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.
• [6] CETi-1. AVANT. Curr Opin Investig Drugs. 2004 Mar;5(3):334-8.
• [7] Safety and tolerability of dalcetrapib. Am J Cardiol. 2009 Jul 1;104(1):82-91.
• [8] Pfizer. Product Development Pipeline. March 31 2009.
• [9] Ds-1442b is a Novel, Potent Cetp Inhibitor That Reduces Atherosclerosis by Hdl Elevation and Non-hdl Reduction. Circulation. 2012; 126: A11806.
• [10] Chromanol derivatives--a novel class of CETP inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):488-91.
• [11] 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.
• [12] 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.