Therapeutic Targets Database
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TTD Target ID: TTDC00130

Target Information
NameLeukotriene A-4 hydrolase    
Type of targetClinical trial target    
SynonymsLTA-4 hydrolase    
LTA-H    
LTA4H    
Leukotriene A(4) hydrolase    
Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase    
Leukotriene A4 hydrolase    
DiseaseInflammation[1]
Leukemia, Myeloid
[ICD9: 208.9   ICD10: C91-C95]
[2][3][4]
Myocardial infarction
[ICD9: 410   ICD10: I21, I22]
[5][6]
Oesophageal cancer
[ICD9: 140-229   ICD10: C00-C96]
[7]
Solid tumors
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[2][3][4]
Drug(s)DG051Phase IIaMyocardial infarction[5][6]
BioChemical ClassHydrolases acting on ether bonds    
EC NumberEC 3.3.2.6
PathwayArachidonic acid metabolism
Metabolic pathways
UniProt IDP09960
PDB Structure1GW6; 1H19; 1HS6; 1SQM; 2R59; 2VJ8; 3B7R; 3B7S; 3B7T; 3B7U; 3CHO; 3CHP; 3CHQ; 3CHR; 3CHS; 3FH5; 3FH7; 3FH8; 3FHE; 3FTS; 3FTU; 3FTV; 3FTW; 3FTX; 3FTY; 3FTZ; 3FU0; 3FU3; 3FU5; 3FU6; 3FUD; 3FUE; 3FUF; 3FUH; 3FUI; 3FUJ; 3FUK; 3FUL; 3FUM; 3FUN; 3U9W; 4DPR.    
FunctionHydrolyzes an epoxide moiety of leukotriene a4 (lta-4) to form leukotriene b4 (ltb-4). The enzyme also has some peptidase activity.    
SequenceMPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDL TIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLT PEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETP DPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETES MLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISH SWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGET HPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSI TTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAK EDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWL RLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVT AMLVGKDLKVD
Related US Patent6,407,140
6,436,973
Target ValidationClick to Find Target Validation Information.    
Inhibitor (4-[8]
(4-fluorophenyl)[9]
(R)-2-[10]
(R)-2-[10]
(R)-2-[8]
(R)-N-benzyl-4-[11]
(R/S)-2-[10]
(R/S)-2-[10]
(R/S)-2-[10]
(S)-2-[10]
1- (2,2'-bithiophen-5-yl)methanamine[9]
1- (4-Phenoxyphenyl)piperazine[8]
1- (4-thiophen-2-ylphenyl)methanamine[9]
1- (pentyloxy)-4-phenoxybenzene[12]
1-[4- (4-Iodophenoxy)phenyl]piperazine[8]
1-[4- (Benzothiazol-2-yloxy)benzyl]piperidin-4-ol[13]
1-butoxy-4-phenoxybenzene[12]
2- (4-Piperidin-1-ylmethylphenoxy)benzothiazole[13]
2- (4-benzylphenoxy)ethanamine[12]
2- (4-phenoxyphenoxy)ethanamine[12]
2- (7-[14]
2-Amino-N-[4- (phenylmethoxy)phenyl]-acetamide[15]
2-[4- (2-Azepan-1-ylethoxy)phenoxy]benzooxazole[13]
2-[4- (2-Azepan-1-ylethoxy)phenoxy]benzothiazole[13]
2-[4- (2-Morpholin-4-ylethoxy)phenoxy]benzooxazole[13]
2-[4- (2-Piperidin-1-ylethyl)phenoxy]benzothiazole[13]
3- (Benzyloxy)Pyridin-2-Amine[16]
4- (2-amino-1,3-thiazol-4-yl)phenol[9]
4- (4-[12]
4- (4-butoxyphenoxy)phenol[12]
4- (4-propoxyphenoxy)phenol[12]
4-Amino-N-[4- (phenylmethoxy)phenyl]butanamide[15]
4-[2- (4-Benzylphenoxy)ethyl]pyridine[8]
4-amino-N-[4- (benzyloxy)phenyl]butanamide[9]
4S-4,5-Diamino-N- (4-phenoxyphenyl)pentanamide[15]
5-[2- (1H-pyrrol-1-yl)ethoxy]-1H-indole[9]
5-[2- (4-hydroxyphenyl)ethyl]benzene-1,3-diol[9]
8 (S)-amino-2[17]
Acetate Ion[16]
Bestatin[18]
DG051[5][6]
Imidazole[18]
JNJ-10392980[13]
N- (pyridin-3-ylmethyl)aniline[9]
N-[4- (benzyloxy)phenyl]glycinamide[9]
N-benzyl-4-[ (2R)-pyrrolidin-2-ylmethoxy]aniline[9]
N-methyl-1- (2-thiophen-2-ylphenyl)methanamine[9]
N1-[4- (Phenylmethoxy)phenyl]-D-aspartamine[15]
N1-[4- (Phenylmethoxy)phenyl]-D-glutamine[15]
N1-[4- (Phenylmethoxy)phenyl]-L-aspartamine[15]
N1-[4- (Phenylmethoxy)phenyl]-L-glutamine[15]
N4-[4- (Phenylmethoxy)phenyl]-L-aspartamine[15]
N5- (4-Phenoxyphenyl)-L-glutamine[15]
N5-[ (4-Phenoxy)-3-pyridyl]-L-glutamamide[15]
N5-[4- (1H-pyrrol-1-yl)phenyl]-L-glutamamide[15]
N5-[4- (2-Oxo-3-phenylpropoxy)phenyl]-L-glutamine[15]
N5-[4- (2-methylphenoxy)phenyl]-L-glutamamide[15]
N5-[4- (2-phenylethoxy)phenyl]-L-glutamine[15]
N5-[4- (3-Phenylpropoxy)phenyl]-L-glutamine[15]
N5-[4- (3-methylphenoxy)phenyl]-L-glutamamide[15]
N5-[4- (4-[15]
N5-[4- (4-methylphenoxy)phenyl]-L-glutamamide[15]
N5-[4- (N-Phenylamino)phenyl]-L-glutamine[15]
N5-[4- (Phenylmethoxy)phenyl]-D-glutamine[15]
N5-[4- (Phenylmethoxy)phenyl]-L-glutamamide[15]
N5-[4- (Phenylmethoxy)phenyl]-L-glutamine[15]
N5-[4-Benzylphenyl]-L-glutamamide[15]
N6-[4- (4-methylphenoxy)phenyl]-L-homoglutamine[15]
SA-6541[19]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Alteration of human leukotriene A4 hydrolase activity after site-directed mutagenesis: serine-415 is a regulatory residue. Biochim Biophys Acta. 1999 May 18;1438(2):199-203. To Reference
Ref 2Aminopeptidase inhibition as a targeted treatment strategy in myeloma. Mol Cancer Ther. 2009 Apr;8(4):762-70. To Reference
Ref 3Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):383-408. To Reference
Ref 4Cancer Res. 2008 Aug 15;68(16):6669-79.CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. To Reference
Ref 5BAY x 1005 attenuates atherosclerosis in apoE/LDLR - double knockout mice. J Physiol Pharmacol. 2007 Sep;58(3):583-8. To Reference
Ref 6Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA. 2005 May 11;293(18):2245-56. To Reference
Ref 7Leukotriene A4 hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin. J Natl Cancer Inst. 2003 Jul 16;95(14):1053-61. To Reference
Ref 8J Med Chem. 2010 Jan 28;53(2):573-85.Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis. To Reference
Ref 9Berman 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 10Bioorg Med Chem Lett. 2010 May 1;20(9):2851-4. Epub 2010 Mar 12.Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds. To Reference
Ref 11J Med Chem. 2009 Aug 13;52(15):4694-715.Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography. To Reference
Ref 12Bioorg Med Chem Lett. 2008 Dec 15;18(24):6549-52. Epub 2008 Oct 14.Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives. To Reference
Ref 13J Med Chem. 2008 Jul 24;51(14):4150-69. Epub 2008 Jun 28.Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. To Reference
Ref 14J Med Chem. 2008 Dec 25;51(24):7882-8.Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching. To Reference
Ref 15Bioorg Med Chem. 2008 May 1;16(9):4963-83. Epub 2008 Mar 20.Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase. 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 Nat Prod. 1996 Oct;59(10):962-4.Isolation and structure of leukotriene-A4 hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus. To Reference
Ref 18Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 19Bioorg Med Chem Lett. 2009 Jan 15;19(2):442-6. Epub 2008 Nov 18.Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors. To Reference



 

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