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Leukotriene C4 synthase

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1391

Nomenclature: Leukotriene C4 synthase

Family: Leukotriene and lipoxin metabolism

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 150 5q35.3 LTC4S leukotriene C4 synthase 2,6
Mouse 4 150 11 B1.3 Ltc4s leukotriene C4 synthase
Rat 4 150 10q22 Ltc4s leukotriene C4 synthase
Previous and Unofficial Names Click here for help
LTC4 synthase
Database Links Click here for help
Alphafold Q16873 (Hs), Q60860 (Mm), Q925U2 (Rn)
BRENDA 4.4.1.20
CATH/Gene3D 1.20.120.550
ChEMBL Target CHEMBL1743183 (Hs), CHEMBL2172 (Rn)
Ensembl Gene ENSG00000213316 (Hs), ENSMUSG00000020377 (Mm), ENSRNOG00000003244 (Rn)
Entrez Gene 4056 (Hs), 17001 (Mm), 114097 (Rn)
Human Protein Atlas ENSG00000213316 (Hs)
KEGG Enzyme 4.4.1.20
KEGG Gene hsa:4056 (Hs), mmu:17001 (Mm), rno:114097 (Rn)
OMIM 246530 (Hs)
Pharos Q16873 (Hs)
RefSeq Nucleotide NM_145867 (Hs)
RefSeq Protein NP_665874 (Hs)
UniProtKB Q16873 (Hs), Q60860 (Mm), Q925U2 (Rn)
Wikipedia LTC4S (Hs)
Enzyme Reaction Click here for help
EC Number: 4.4.1.20 LTC4 = glutathione + LTA4

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TK05 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.2 pKi 3
⤷ pKi 8.2 (Ki 6x10-9 M) [3]
Description: Using isolated human enzyme.
AZD9898 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 9.5 pIC50 5,7
⤷ pIC50 9.5 (IC50 2.89x10-10 M) [5,7]
Description: IC50 vs human recombinant purified LTC4 synthase determined by determination of inhibition of LTC4 methyl ester product formation in vitro
example 36 [WO2016177845] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 7
⤷ pIC50 8.1 (IC50 9x10-9 M) [7]
compound 39 [PMID: 23623673] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.5 pIC50 8
⤷ pIC50 <5.5 (IC50 >3x10-6 M) [8]
Immunopharmacology Comments
The role of leukotriene C4 synthase (LTC4S) in the production of cysteinyl leukotrienes (cys-LTs) which are potent proinflammatory mediators and bronchoconstrictors implicated in airway inflammation in conditions such as asthma [1,4], makes LTC4S a prominent target for pharmaceutical intervention in relevant diseases [3,7].

References

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1. Bigby TD. (2000) The leukotriene C(4) synthase gene and asthma. Am J Respir Cell Mol Biol, 23 (3): 273-6. [PMID:10970815]

2. Bigby TD, Hodulik CR, Arden KC, Fu L. (1996) Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35. Mol Med, 2 (5): 637-46. [PMID:8898379]

3. Kleinschmidt TK, Haraldsson M, Basavarajappa D, Lundeberg E, Thulasingam M, Ekoff M, Fauland A, Lehmann C, Kahnt AS, Lindbom L et al.. (2015) Tandem Benzophenone Amino Pyridines, Potent and Selective Inhibitors of Human Leukotriene C4 Synthase. J Pharmacol Exp Ther, 355 (1): 108-16. [PMID:26283693]

4. MacDonald CA, Bushnell EA, Gauld JW, Boyd RJ. (2014) The catalytic formation of leukotriene C4: a critical step in inflammatory processes. Phys Chem Chem Phys, 16 (30): 16284-9. [PMID:24974917]

5. Munck Af Rosenschöld M, Johannesson P, Nikitidis A, Tyrchan C, Chang HF, Rönn R, Chapman D, Ullah V, Nikitidis G, Glader P et al.. (2019) Discovery of the Oral Leukotriene C4 Synthase Inhibitor (1S,2S)-2-({5-[(5-Chloro-2,4-difluorophenyl)(2-fluoro-2-methylpropyl)amino]-3-methoxypyrazin-2-yl}carbonyl)cyclopropanecarboxylic Acid (AZD9898) as a New Treatment for Asthma. J Med Chem, 62 (17): 7769-7787. [PMID:31415176]

6. Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, Austen KF, Lam BK. (1996) Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. J Biol Chem, 271 (19): 11356-61. [PMID:8626689]

7. Ronn R, Lindh CJ, Ringberg E, Andersson EHB, Nilsson P, Schall WR, Munk af RM, Nikitidis A, Nikitidis G, Johannesson PJ et al.. (2016) Cyclopropane carboxylic acid derivatives and pharmaceutical uses thereof. Patent number: WO2016177845. Assignee: Astrazeneca Ab. Priority date: 06/05/2015. Publication date: 10/11/2016.

8. Shiro T, Kakiguchi K, Takahashi H, Nagata H, Tobe M. (2013) 7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors. Bioorg Med Chem, 21 (11): 2868-78. [PMID:23623673]

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