Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDS00143

Target Information
NameCholinesterase    
Type of targetSuccessful target    
SynonymsAcylcholine acylhydrolase    
BuChE    
Butyrylcholine esterase    
Butyrylcholinesterase    
Choline esterase II    
Pseudocholinesterase    
DiseaseAlzheimer's disease
[ICD9: 331.0   ICD10: G30]
[1][2]
Schizophrenia
[ICD9: 295   ICD10: F20]
[3]
Drug(s)Echothiophate IodideApprovedChronic glaucoma[4]
Hexafluronium bromideApprovedSpasms, Pain[5]
BioChemical ClassHydrolases acting on ester bonds    
EC NumberEC 3.1.1.8
UniProt IDP06276
PDB Structure1EHO; 1EHQ; 1KCJ; 1P0I; 1P0M; 1P0P; 1P0Q; 1XLU; 1XLV; 1XLW; 2J4C; 2PM8; 2WID; 2WIF; 2WIG; 2WIJ; 2WIK; 2WIL; 2WSL; 2XMB; 2XMC; 2XMD; 2XMG; 2XQF; 2XQG; 2XQI; 2XQJ; 2XQK; 2Y1K; 3DJY; 3DKK; 3O9M; 4AQD; 4AXB; 4B0O; 4B0P; 4BBZ; 4BDS.    
SequenceMHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIP YAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDC LYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALG FLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPG SHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEI LLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVY GAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDV VGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLER RDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMT KLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCV GL
Related US Patent6,498,255
Target ValidationClick to Find Target Validation Information.    
Inhibitor (+/-)-DEBROMOFLUSTRAMINE B[6]
(+/-)-huprineY hydrochloride[7]
(-)-Cymserine[8]
(-)-DEBROMOFLUSTRAMINE B[6]
(-)-Phenethylcymserine[8]
(-)-Phenserine[8]
(-)-Tolserine[8]
(1'H-Phenothiazin-1'-yl)[9]
(10H-phenothiazin-10-yl)[10]
(10H-phenothiazin-10-yl)[10]
(10H-phenothiazin-10-yl)[10]
(10H-phenothiazin-10-yl)[10]
(1R)-MENTHYL HEXYL PHOSPHONATE GROUP[11]
(1S)-MENTHYL HEXYL PHOSPHONATE GROUP[11]
1,2-NAPHTHOQUINONE[12]
1,2-indanedione[12]
3-phenyl-cyclosal-d4TMP[13]
3-sal-cyclosal-d4TMP[13]
5-methyl-cyclosal-d4TMP[13]
6-chlorotacrine hydrochloride[14]
ACENAPHTHOQUINONE[12]
AS-1397[15]
Alpha-D-Mannose[16]
BENZOQUINONE[17]
Beta-D-Mannose[16]
Bis-7-tacrine[18]
Butanoic Acid[16]
Butyrylthiocholine[19]
CAPROCTAMINE[20]
CHF-2819[21]
CHLORANIL[17]
Caproctamine HCl[22]
Cymserine[2]
DEMETHYLDEBROMOFLUSTRAMINE B[6]
DODECANESULFONATE ION[11]
Diethylphosphono Group[16]
ETHYL HYDROGEN DIETHYLAMIDOPHOSPHATE[11]
Echothiophate Iodide[4]
Ethyl Dihydrogen Phosphate[16]
Fucose[16]
GALANTAMINE HYDROBROMIDE[23]
HALOXYSTEROL A[24]
HALOXYSTEROL B[24]
HEPTYPHYSOSTIGMINE[25]
Hexafluronium bromide[5]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
Huprine-Tacrine Heterodimer[26]
LAWSARITOL[24]
LIPOCRINE[27]
MEMOQUIN[27]
MEPTAZINOL[28]
MF-8623[2]
Methyl Phosphinic Acid[16]
Monoisopropyl Ester Phosphonic Acid Group[16]
Morpholino (1'H-phenothiazin-1'-yl)methanone[9]
N- (Adamant-1-yl)-1'H-phenothiazine-1'-carboxamide[9]
NOSTOCARBOLINE[29]
NSC-23180[12]
PHENSERINE[30]
TOLSERINE[25]
VAGANINE D[31]
XANTHOSTIGMINE[32]
anthracen-10-yl (10H-phenothiazin-10-yl)methanone[10]
bis-cyclosal-d4TMP[13]
cyclosal-d4TMP[13]
haloxysterol C[24]
haloxysterol D[24]
huprine X[33]
iso-OMPA[34]
m-tolyl 10H-phenothiazine-10-carboxylate[35]
methyl 10H-phenothiazine-10-carboxylate[35]
p-tolyl 10H-phenothiazine-10-carboxylate[35]
phenanthrene-9,10-dione[12]
phenyl 10H-phenothiazine-10-carboxylate[35]
tert-butyl 10H-phenothiazine-10-carboxylate[35]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Current drugs and future hopes in the treatment of Alzheimer's disease. J Neural Transm Suppl. 2002;(62):149-64. To Reference
Ref 2A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase. Curr Med Res Opin. 2001;17(3):159-65. To Reference
Ref 3Differential distribution of butyrylcholinesterase and acetylcholinesterase in the human thalamus. J Comp Neurol. 2003 Aug 11;463(1):25-43. To Reference
Ref 4H-7 effect on outflow facility after trabecular obstruction following long-term echothiophate treatment in monkeys. Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2732-6. To Reference
Ref 5Synergistic effect of acidosis and succinylcholine-induced hyperkalemia in spinal cord transected rats. Acta Anaesthesiol Scand. 1984 Feb;28(1):87-90. To Reference
Ref 6J Med Chem. 2008 Sep 11;51(17):5271-84. Epub 2008 Aug 8.Synthesis and biological evaluation of (-)- and (+)-debromoflustramine B and its analogues as selective butyrylcholinesterase inhibitors. To Reference
Ref 7J Med Chem. 2006 Nov 16;49(23):6833-40.Binding of 13-amidohuprines to acetylcholinesterase: exploring the ligand-induced conformational change of the gly117-gly118 peptide bond in the oxyanion hole. To Reference
Ref 8Bioorg. Med. Chem. 18(13):4687-4693 (2010) To Reference
Ref 9Bioorg Med Chem. 2010 Mar 15;18(6):2232-44. Epub 2010 Feb 4.Differential binding of phenothiazine urea derivatives to wild-type human cholinesterases and butyrylcholinesterase mutants. To Reference
Ref 10Bioorg Med Chem. 2007 Oct 1;15(19):6367-78. Epub 2007 Jul 6.Selective reversible inhibition of human butyrylcholinesterase by aryl amide derivatives of phenothiazine. To Reference
Ref 11Berman 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 12J 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 13J Med Chem. 2007 Mar 22;50(6):1335-46. Epub 2007 Mar 1.Bis-cycloSal-d4T-monophosphates: drugs that deliver two molecules of bioactive nucleotides. To Reference
Ref 14J Med Chem. 2009 Sep 10;52(17):5365-79.Pyrano[3,2-c]quinoline-6-chlorotacrine hybrids as a novel family of acetylcholinesterase- and beta-amyloid-directed anti-Alzheimer compounds. To Reference
Ref 15J Med Chem. 2006 Dec 14;49(25):7540-4.Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase. To Reference
Ref 16Overington 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 17J 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 18Bioorg Med Chem Lett. 2010 Jun 15;20(12):3606-9. Epub 2010 Apr 28.Design, synthesis and evaluation of 2,4-disubstituted pyrimidines as cholinesterase inhibitors. To Reference
Ref 19Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 20J Med Chem. 2008 Nov 27;51(22):7308-12.Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone. 4. Further investigation on the inner spacer. To Reference
Ref 21J Med Chem. 2005 Feb 24;48(4):986-94.Novel anticholinesterases based on the molecular skeletons of furobenzofuran and methanobenzodioxepine. To Reference
Ref 22J Med Chem. 2007 Oct 4;50(20):4882-97. Epub 2007 Sep 13.Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease. To Reference
Ref 23Bioorg Med Chem Lett. 2010 Jun 1;20(11):3254-8. Epub 2010 Apr 18.Synthesis of 4-[(diethylamino)methyl]-phenol derivatives as novel cholinesterase inhibitors with selectivity towards butyrylcholinesterase. To Reference
Ref 24Bioorg Med Chem Lett. 2006 Feb;16(3):573-80. Epub 2005 Nov 7.Isolation and cholinesterase-inhibition studies of sterols from Haloxylon recurvum. To Reference
Ref 25J Med Chem. 2006 Apr 6;49(7):2174-85.Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. To Reference
Ref 26J Med Chem. 2005 Mar 24;48(6):1701-4.Synthesis and pharmacological evaluation of huprine-tacrine heterodimers: subnanomolar dual binding site acetylcholinesterase inhibitors. To Reference
Ref 27J Med Chem. 2009 Dec 10;52(23):7883-6.Toward a rational design of multitarget-directed antioxidants: merging memoquin and lipoic acid molecular frameworks. To Reference
Ref 28J Med Chem. 2008 Apr 10;51(7):2027-36. Epub 2008 Mar 12.Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-beta aggregation. To Reference
Ref 29J Nat Prod. 2005 Dec;68(12):1793-5.Nostocarboline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A. To Reference
Ref 30Bioorg Med Chem Lett. 2010 Mar 1;20(5):1532-4. Epub 2010 Jan 25.Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities. To Reference
Ref 31J Nat Prod. 2001 Jun;64(6):842-4.Steroidal alkaloids from the leaves of Sarcococca coriacea of Nepalese origin. To Reference
Ref 32J Med Chem. 1998 Oct 8;41(21):3976-86.Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives. To Reference
Ref 33J Med Chem. 2006 Jun 1;49(11):3421-5.Discovery of huperzine A-tacrine hybrids as potent inhibitors of human cholinesterases targeting their midgorge recognition sites. To Reference
Ref 34J Med Chem. 2008 Oct 23;51(20):6400-9. Epub 2008 Sep 26.Isosorbide-2-carbamate esters: potent and selective butyrylcholinesterase inhibitors. To Reference
Ref 35J Med Chem. 2008 Jul 24;51(14):4200-12. Epub 2008 Jun 21.Carbamates with differential mechanism of inhibition toward acetylcholinesterase and butyrylcholinesterase. To Reference



 

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