Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDR00274

Target Information
NameLiver carboxylesterase    
Type of targetResearch target    
SynonymsACAT    
Acyl coenzyme A:cholesterol acyltransferase    
Brain carboxylesterase hBr1    
HCE1    
HMSE    
Human carboxylesterase 1    
Monocyte/macrophage serine esterase    
Serine esterase 1    
DiseaseAlzheimer's disease
[ICD9: 331.0   ICD10: G30]
[1]
Atherosclerosis
[ICD9: 414.0, 440   ICD10: I70]
[1][2]
Cardiovascular disease, unspecified
[ICD9: 390-459   ICD10: I00-I99]
[3]
Cocaine overdose
[ICD9: 304.2   ICD10: F14.2]
[4]
Hypercholesterolaemia[1]
Protection against chemical weapons like Sarin, Soman and VX gas[4]
BioChemical ClassHydrolases acting on ester bonds    
EC NumberEC 3.1.1.1
PathwayAlkaloid biosynthesis II
Drug metabolism - other enzymes
UniProt IDP23141
PDB Structure1MX1; 1MX5; 1MX9; 1YA4; 1YA8; 1YAH; 1YAJ; 2DQY.    
FunctionInvolved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl coa ester.    
SequenceMWLRAFILATLSASAAWGHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPL GPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLN IYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWGFFST GDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLF HRAISESGVALTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLK MKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIP MQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDL IADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPF LKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLK DKEVAFWTNLFAKKAVEKPPQTEHIEL
Related US Patent6,444,691
Target ValidationClick to Find Target Validation Information.    
Inhibitor (1R)-1,2,2-TRIMETHYLPROPYL [5]
(E)-Octadec-9-enoic acid phenylamide[6]
1,1,1-trifluoro-3- (hexylsulfinyl)propan-2-one[7]
1,1,1-trifluoro-3- (hexylsulfonyl)propan-2-one[7]
1,1,1-trifluoro-3- (hexylthio)propan-2-one[7]
1,1,1-trifluoro-3- (octylsulfinyl)propan-2-one[7]
1,1,1-trifluoro-3- (octylsulfonyl)propan-2-one[7]
1,1,1-trifluoro-3- (octylthio)propan-2-one[7]
1,1,1-trifluorododecan-2-one[7]
1,10-phenanthroline-5,6-dione[8]
1,2-Bis- (2-chloro-phenyl)-ethane-1,2-dione[9]
1,2-Bis- (3-methoxy-phenyl)-ethane-1,2-dione[9]
1,2-Bis- (3-nitro-phenyl)-ethane-1,2-dione[9]
1,2-Bis- (4-bromo-phenyl)-ethane-1,2-dione[9]
1,2-Bis- (4-chloro-phenyl)-ethane-1,2-dione[9]
1,2-Bis- (4-methoxy-phenyl)-ethane-1,2-dione[9]
1,2-Di-naphthalen-2-yl-ethane-1,2-dione[10]
1,2-Di-p-tolyl-ethane-1,2-dione[9]
1,2-NAPHTHOQUINONE[8]
1,2-bis (2,3,4-trifluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2,3,4-trifluorophenyl)ethane-1,2-dione[11]
1,2-bis (2,3,5-trifluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2,3,5-trifluorophenyl)ethane-1,2-dione[11]
1,2-bis (2,3,6-trifluorophenyl)ethane-1,2-dione[11]
1,2-bis (2,3-difluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2,3-fluorophenyl)ethane-1,2-dione[11]
1,2-bis (2,4-difluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2,4-difluorophenyl)ethane-1,2-dione[11]
1,2-bis (2,5-difluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2,5-difluorophenyl)ethane-1,2-dione[11]
1,2-bis (2,6-difluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2,6-difluorophenyl)ethane-1,2-dione[11]
1,2-bis (2-fluorophenyl)-2-hydroxyethanone[11]
1,2-bis (2-fluorophenyl)ethane-1,2-dione[11]
1,2-bis (3,4,5-trifluorophenyl)-2-hydroxyethanone[11]
1,2-bis (3,4,5-trifluorophenyl)ethane-1,2-dione[11]
1,2-bis (3,4-difluorophenyl)-2-hydroxyethanone[11]
1,2-bis (3,4-difluorophenyl)ethane-1,2-dione[11]
1,2-bis (3,5-difluorophenyl)-2-hydroxyethanone[11]
1,2-bis (3,5-difluorophenyl)ethane-1,2-dione[11]
1,2-bis (3-fluorophenyl)-2-hydroxyethanon[11]
1,2-bis (3-fluorophenyl)ethane-1,2-dione[11]
1,2-bis (4-fluorophenyl)ethane-1,2-dione[11]
1,2-dicyclohexylethane-1,2-dione[8]
1,2-indanedione[8]
1- (2-bromoethyl)-1H-indole-2,3-dione[12]
1- (2-iodoethyl)-1H-indole-2,3-dione[12]
1- (3,4-Dimethyl-phenyl)-2-phenyl-ethane-1,2-dione[9]
1- (3,4-dichlorobenzyl)-1H-indole-2,3-dione[12]
1- (4-Chloro-phenyl)-2-p-tolyl-ethane-1,2-dione[9]
1- (4-Chloro-phenyl)-2-phenyl-ethane-1,2-dione[9]
1- (4-Methoxy-phenyl)-2-phenyl-ethane-1,2-dione[9]
1- (4-Nitro-phenyl)-2-phenyl-ethane-1,2-dione[9]
1- (4-chlorobenzyl)-1H-indole-2,3-dione[12]
1-Phenyl-2-p-tolyl-ethane-1,2-dione[9]
1-Phenyl-propane-1,2-dione[9]
1-benzyl-1H-indole-2,3-dione[12]
1-butyryl-1H-indole-2,3-dione[12]
1-dodecyl-1H-indole-2,3-dione[12]
1-hexadecyl-1H-indole-2,3-dione[12]
1-methyl-1H-indole-2,3-dione[12]
1-phenyl-1H-indole-2,3-dione[12]
1-propionyl-1H-indole-2,3-dione[12]
11,12-dihydro-dibenzo[a,e]cyclooctene-5,6-dione[8]
2,2-Dimethoxy-1,2-diphenyl-ethanone[9]
2,2-dimethyl-3-methyleneheptadecane[7]
2-methoxy-3,4-methylenedioxybenzophenone[13]
3,4,5,6-Tetrachloro-[1,2]benzoquinone[9]
3,5-Di-tert-butyl-[1,2]benzoquinone[9]
3- (butylsulfinyl)-1,1,1-trifluoropropan-2-one[7]
3- (butylthio)-1,1,1-trifluoropropan-2-one[7]
3- (decylsulfinyl)-1,1,1-trifluoropropan-2-one[7]
3- (decylsulfonyl)-1,1,1-trifluoropropan-2-one[7]
3- (decylthio)-1,1,1-trifluoropropan-2-one[7]
3- (dodecylsulfinyl)-1,1,1-trifluoropropan-2-one[7]
3- (dodecylsulfonyl)-1,1,1-trifluoropropan-2-one[7]
4,5-dichloro-1H-indole-2,3-dione[12]
4,6-dichloro-1H-indole-2,3-dione[12]
4,7-dichloro-1H-indole-2,3-dione[12]
4- (2-Oxo-2-phenyl-acetyl)-benzoic acid[9]
4-Piperidino-Piperidine[5]
4-chloro-1H-indole-2,3-dione[12]
4-chloro-7-methyl-1H-indole-2,3-dione[12]
5,6-dinitroacenaphthoquinone[8]
5,7-dichloro-1H-indole-2,3-dione[12]
5- (trifluoromethoxy)-1H-indole-2,3-dione[12]
5-chloro-1H-indole-2,3-dione[12]
6,7-dichloro-1H-indole-2,3-dione[12]
6-bromo-5-methyl-1H-indole-2,3-dione[12]
7- (trifluoromethyl)-1H-indole-2,3-dione[12]
7-chloro-1H-indole-2,3-dione[12]
ACENAPHTHOQUINONE[8]
Alpha-D-Mannose[14]
Avasimibe[3]
BENZIL[7]
BENZOIN[11]
CHLORANIL[9]
CI-976[15]
Cholic Acid[14]
Dibutyl 2,2,2-trifluoro-1-phenylethyl phosphate[16]
Diethyl 2,2,2-trifluoro-1-phenylethyl phosphate[16]
Dimethyl 2,2,2-trifluoro-1-phenylethyl phosphate[16]
Heptane-2,3-dione[9]
N-Methylnaloxonium[17]
NSC-23180[8]
O-Sialic Acid[5]
Oleic Acid Anilide[13]
PACTIMIBE[18]
PYRIPYROPENE A[6]
SCH-48375,   SCH-48678[19]
SM-32504[20]
Thenoyltrifluoroacetone[21]
acenanthrene-9,10-dione[8]
phenanthrene-9,10-dione[8]
thieno[3,2-e][1]benzothiophene-4,5-dione[8]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Selective ACAT inhibitors as promising antihyperlipidemic, antiathero-sclerotic and anti-Alzheimer drugs. Mini Rev Med Chem. 2003 Sep;3(6):576-84. To Reference
Ref 2Inhibition of acyl coenzyme A-cholesterol acyltransferase: a possible treatment of atherosclerosis? Curr Atheroscler Rep. 2002 Jan;4(1):65-70. To Reference
Ref 3New advances in lipid-modifying therapies for reducing cardiovascular risk. Cardiology. 2002;97(2):59-66. To Reference
Ref 4Human carboxylesterase 1: from drug metabolism to drug discovery. Biochem Soc Trans. 2003 Jun;31(Pt 3):620-4. To Reference
Ref 5Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 6Bioorg Med Chem Lett. 2004 Aug 16;14(16):4277-80.Acyl-CoA: cholesterol acyltransferase inhibitory activities of fatty acid amides isolated from Mylabris phalerate Pallas. To Reference
Ref 7Bioorg Med Chem. 2008 Feb 15;16(4):2114-30. Epub 2007 Nov 26.Influence of sulfur oxidation state and steric bulk upon trifluoromethyl ketone (TFK) binding kinetics to carboxylesterases and fatty acid amide hydrolase (FAAH). To Reference
Ref 8J Med Chem. 2007 Nov 15;50(23):5727-34. Epub 2007 Oct 17.Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. To Reference
Ref 9J Med Chem. 2005 Apr 21;48(8):2906-15.Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases. To Reference
Ref 10J Med Chem. 2005 Aug 25;48(17):5543-50.Inhibition of carboxylesterases by benzil (diphenylethane-1,2-dione) and heterocyclic analogues is dependent upon the aromaticity of the ring and the flexibility of the dione moiety. To Reference
Ref 11Bioorg Med Chem. 2007 Jun 1;15(11):3801-17. Epub 2007 Mar 12.Analysis of the inhibition of mammalian carboxylesterases by novel fluorobenzoins and fluorobenzils. To Reference
Ref 12J Med Chem. 2007 Apr 19;50(8):1876-85. Epub 2007 Mar 23.Selective inhibition of carboxylesterases by isatins, indole-2,3-diones. To Reference
Ref 13J Nat Prod. 2006 May;69(5):853-5.Phenolic compounds from the roots of Lindera fruticosa. To Reference
Ref 14Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 15Acyl-coenzyme A:cholesterol-acyltransferase (ACAT) inhibitors modulate monocyte adhesion to aortic endothelial cells. Atherosclerosis. 1995 Jan 6;112(1):7-17. To Reference
Ref 16Bioorg Med Chem Lett. 2009 Oct 1;19(19):5528-30. Epub 2009 Aug 21.Synthesis of organophosphates with fluorine-containing leaving groups as serine esterase inhibitors with potential for Alzheimer disease therapeutics. To Reference
Ref 17Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 18J Med Chem. 2008 Aug 14;51(15):4823-33. Epub 2008 Jul 12.Novel indoline-based acyl-CoA:cholesterol acyltransferase inhibitor with antiperoxidative activity: improvement of physicochemical properties and biological activities by introduction of carboxylic acid. To Reference
Ref 19J Med Chem. 1994 Jun 10;37(12):1733-6.2-Azetidinones as inhibitors of cholesterol absorption. To Reference
Ref 20Bioorg Med Chem Lett. 2006 Jan 1;16(1):44-8. Epub 2005 Oct 18.Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility. To Reference
Ref 21Zhang JG, Fariss MW: Thenoyltrifluoroacetone, a potent inhibitor of carboxylesterase activity. Biochem Pharmacol. 2002 Feb 15;63(4):751-4. To Reference



 

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Professor in Department of Pharmacy
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