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target has curated data in GtoImmuPdb
Target id: 1395
Nomenclature: Leukotriene A4 hydrolase
Family: Leukotriene and lipoxin metabolism, M1: Aminopeptidase N, Hydrolases
Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 611 | 12q23.1 | LTA4H | leukotriene A4 hydrolase | |
Mouse | - | 611 | 10 C2 | Lta4h | leukotriene A4 hydrolase | |
Rat | - | 610 | 7q13 | Lta4h | leukotriene A4 hydrolase |
Database Links ![]() |
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Specialist databases | |
MEROPS | M01.004 (Hs) |
Other databases | |
BRENDA | 3.3.2.6 |
ChEMBL Target | CHEMBL4618 (Hs), CHEMBL3738 (Mm), CHEMBL2400 (Rn) |
Ensembl Gene | ENSG00000111144 (Hs), ENSMUSG00000015889 (Mm), ENSRNOG00000004494 (Rn) |
Entrez Gene | 4048 (Hs), 16993 (Mm), 299732 (Rn) |
Human Protein Atlas | ENSG00000111144 (Hs) |
KEGG Enzyme | 3.3.2.6 |
KEGG Gene | hsa:4048 (Hs), mmu:16993 (Mm), rno:299732 (Rn) |
OMIM | 151570 (Hs) |
Pharos | P09960 (Hs) |
RefSeq Nucleotide | NM_001256643 (Hs), NM_001256644 (Hs), NM_000895 (Hs), NM_008517 (Mm), NM_001030031 (Rn) |
RefSeq Protein | NP_000886 (Hs), NP_001243573 (Hs), NP_001243572 (Hs), NP_032543 (Mm), NP_001025202 (Rn) |
SynPHARM |
13735 (in complex with bestatin) 83483 (in complex with compound 1a [PMID: 25692029]) 78669 (in complex with DG-051) |
UniProtKB | P09960 (Hs), P24527 (Mm), P30349 (Rn) |
Wikipedia | LTA4H (Hs) |
Selected 3D Structures ![]() |
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Enzyme Reaction ![]() |
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Download all structure-activity data for this target as a CSV file
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Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||
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Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
LTA4H is an established immunomodulatory target. LTA4H exhibits opposing pro- and anti-inflammatory functions: epoxide hydrolase (EH) activity which catalyses the hydrolysis of leukotriene A4 to leukotriene B4, which promotes neutrophilic inflammation, and aminopeptidase (AP) activity which catalyses the hydrolysis of the tripeptide proline-glycine-proline (PGP) to promote resolution of neutrophilic infiltration. Expression has been identified in some cancer cells, where it may play a role in the development and progression of cancers associated with chronic inflammation, suggesting that LTA4H inhibitors may have efficacy as anti-cancer therapeutics [3]. X-ray structures revealing the dynamic domain movements taking place upon substrate (LTA4) interaction will allow for more rational drug design [8]. On the other hand, activators of LTA4H AP activity have potential to enhance the anti-inflammatory properties of the enzyme [4]. |
Immuno Process Associations | |||||||||
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1. Bollbuck B, Merkert C, Miltz W, Roehn T. (2015) Heteroaryl butanoic acid derivatives as lta4h inhibitors. Patent number: WO2015092740A1. Assignee: Novartis Ag. Priority date: 20/12/2013. Publication date: 25/06/2015.
2. Bonnard E, Poras H, Nadal X, Maldonado R, Fournié-Zaluski MC, Roques BP. (2015) Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain. Pharmacol Res Perspect, 3 (2): e00116. [PMID:25692029]
3. Chen X, Wang S, Wu N, Yang CS. (2004) Leukotriene A4 hydrolase as a target for cancer prevention and therapy. Curr Cancer Drug Targets, 4 (3): 267-83. [PMID:15134534]
4. Lee KH, Petruncio G, Shim A, Burdick M, Zhang Z, Shim YM, Noble SM, Paige M. (2019) Effect of Modifier Structure on the Activation of Leukotriene A4 Hydrolase Aminopeptidase Activity. J. Med. Chem., 62 (23): 10605-10616. [PMID:31751136]
5. Orning L, Krivi G, Fitzpatrick FA. (1991) Leukotriene A4 hydrolase. Inhibition by bestatin and intrinsic aminopeptidase activity establish its functional resemblance to metallohydrolase enzymes. J. Biol. Chem., 266 (3): 1375-8. [PMID:1846352]
6. Penning TD, Chandrakumar NS, Chen BB, Chen HY, Desai BN, Djuric SW, Docter SH, Gasiecki AF, Haack RA, Miyashiro JM et al.. (2000) Structure-activity relationship studies on 1-[2-(4-Phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A(4) (LTA(4)) hydrolase. J. Med. Chem., 43 (4): 721-35. [PMID:10691697]
7. Sandanayaka V, Mamat B, Mishra RK, Winger J, Krohn M, Zhou LM, Keyvan M, Enache L, Sullins D, Onua E et al.. (2010) 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. J. Med. Chem., 53 (2): 573-85. [PMID:19950900]
8. Stsiapanava A, Samuelsson B, Haeggström JZ. (2017) Capturing LTA4 hydrolase in action: Insights to the chemistry and dynamics of chemotactic LTB4 synthesis. Proc. Natl. Acad. Sci. U.S.A., 114 (36): 9689-9694. [PMID:28827365]
9. Tholander F, Muroya A, Roques BP, Fournié-Zaluski MC, Thunnissen MM, Haeggström JZ. (2008) Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design. Chem. Biol., 15 (9): 920-9. [PMID:18804029]