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5-LOX

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1385

Nomenclature: 5-LOX

Family: Lipoxygenases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 674 10q11.21 ALOX5 arachidonate 5-lipoxygenase
Mouse - 674 6 53.79 cM Alox5 arachidonate 5-lipoxygenase
Rat - 673 4q42 Alox5 arachidonate 5-lipoxygenase
Previous and Unofficial Names Click here for help
ALOX5 | 5-lipoxygenase | 5-LO | arachidonate 5-lipoxygenase
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 1.13.11.34 Arachidonic acid + O2 = LTA4 + H2O
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
arachidonic acid Substrate is endogenous in the given species Hs - -
Endogenous inhibitor
Protein kinase A-mediated phosphorylation  [9]

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Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
5-LOX activating protein {Sp: Human} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Hs Activation - -
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CJ13610 Small molecule or natural product Hs Inhibition 7.2 pIC50 6
pIC50 7.2 (IC50 7x10-8 M) [6]
2-TEDC Small molecule or natural product Rn Inhibition 7.1 pIC50 4
pIC50 7.1 (IC50 9x10-8 M) [4]
Description: Inhibitory activity against 5-LOX in rat polymorphonuclear leukocytes
BW B70C Small molecule or natural product Hs Inhibition 6.7 pIC50 13
pIC50 6.7 [13]
PF-04191834 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 10
pIC50 6.6 (IC50 2.29x10-7 M) [10]
zileuton Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Inhibition 5.8 – 6.5 pIC50 2,14,16
pIC50 6.5 (IC50 3x10-7 M) [14]
Description: Inhibition of recombinant 5-LOX in vitro.
pIC50 6.4 (IC50 4x10-7 M) [2]
Description: Inhibition of leukotriene B4 biosynthesis by human polymorphonuclear leukocytes.
pIC50 5.8 (IC50 1.5x10-6 M) [16]
Description: Inhibition of purified recombinant human 5-LOX in a cell-free assay.
5-LOX inhibitor 2m [PMID: 30199704] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 16
pIC50 6.1 (IC50 9x10-7 M) [16]
Description: In vitro biochemical inhibitory activity.
View species-specific inhibitor tables
Immunopharmacology Comments
5-LOX is included in GtoImmuPdb because of its involvement in eicosanoid turnover and because it is being actively pursued as a molecular target for the development of novel anti-inflammatory therapeutics [16]. 5-LOX inhibitors with dual activity at other targets within the arachadonic acid/eicosanoid metabolic pathway (e.g. COX1/2, soluble epoxide hydrolase, mPGES1) are also being designed as more effective anti-inflammatory agents [1,3,5,7-8,11-12,15].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 11 GO processes
GO:0002232 leukocyte chemotaxis involved in inflammatory response IMP
GO:0002523 leukocyte migration involved in inflammatory response ISS
GO:0002526 acute inflammatory response ISO
GO:0006954 inflammatory response IMP
GO:0036336 dendritic cell migration ISS
GO:0043312 neutrophil degranulation TAS
GO:0050727 regulation of inflammatory response IMP
GO:0050728 negative regulation of inflammatory response IDA
GO:0106014 regulation of inflammatory response to wounding ISS
GO:1900015 regulation of cytokine production involved in inflammatory response ISS
click arrow to show/hide IEA associations
GO:0002540 leukotriene production involved in inflammatory response IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
GO:0035655 interleukin-18-mediated signaling pathway TAS
GO:1900015 regulation of cytokine production involved in inflammatory response ISS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Asthma, susceptibility to
Disease Ontology: DOID:2841
OMIM: 600807
Role: 

References

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1. Abdelgawad MA, Labib MB, Ali WAM, Kamel G, Azouz AA, El-Nahass ES. (2018) Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies. Bioorg Chem, 78: 103-114. [PMID:29550530]

2. Carter GW, Young PR, Albert DH, Bouska J, Dyer R, Bell RL, Summers JB, Brooks DW. (1991) 5-lipoxygenase inhibitory activity of zileuton. J Pharmacol Exp Ther, 256 (3): 929-37. [PMID:1848634]

3. Chaaban I, Rizk OH, Ibrahim TM, Henen SS, El-Khawass EM, Bayad AE, El-Ashmawy IM, Nematalla HA. (2018) Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives. Bioorg Chem, 78: 220-235. [PMID:29602046]

4. Cho H, Ueda M, Tamaoka M, Hamaguchi M, Aisaka K, Kiso Y, Inoue T, Ogino R, Tatsuoka T, Ishihara T et al.. (1991) Novel caffeic acid derivatives: extremely potent inhibitors of 12-lipoxygenase. J Med Chem, 34 (4): 1503-5. [PMID:2016727]

5. El-Nagar MKS, Abdu-Allah HHM, Salem OIA, Kafafy AN, Farghaly HSM. (2018) Novel N-substituted 5-aminosalicylamides as dual inhibitors of cyclooxygenase and 5-lipoxygenase enzymes: Synthesis, biological evaluation and docking study. Bioorg Chem, 78: 80-93. [PMID:29550533]

6. Fischer L, Steinhilber D, Werz O. (2004) Molecular pharmacological profile of the nonredox-type 5-lipoxygenase inhibitor CJ-13,610. Br J Pharmacol, 142 (5): 861-8. [PMID:15197110]

7. Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerstmeier J, Liening S, Werner M et al.. (2017) Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase. Sci Rep, 7 (1): 9398. [PMID:28839250]

8. Liu Y, Duan C, Chen H, Wang C, Liu X, Qiu M, Tang H, Zhang F, Zhou X, Yang J. (2018) Inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate crystal-induced inflammation. Toxicol Appl Pharmacol, 351: 1-11. [PMID:29763636]

9. Luo M, Jones SM, Phare SM, Coffey MJ, Peters-Golden M, Brock TG. (2004) Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem, 279 (40): 41512-20. [PMID:15280375]

10. Masferrer JL, Zweifel BS, Hardy M, Anderson GD, Dufield D, Cortes-Burgos L, Pufahl RA, Graneto M. (2010) Pharmacology of PF-4191834, a novel, selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain. J Pharmacol Exp Ther, 334 (1): 294-301. [PMID:20378715]

11. Nandha B, Ramareddy SA, Kuntal H. (2018) Synthesis of substituted fluorobenzimidazoles as inhibitors of 5-lipoxygenase and soluble epoxide hydrolase for anti-inflammatory activity. Arch Pharm (Weinheim), 351 (6): e1800030. [PMID:29732612]

12. P JJ, Manju SL, Ethiraj KR, Elias G. (2018) Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: A structure-based approach. Eur J Pharm Sci, 121: 356-381. [PMID:29883727]

13. Payne AN, Jackson WP, Salmon JA, Nicholls A, Yeadon M, Garland LG. (1991) Hydroxamic acids and hydroxyureas as novel, selective 5-lipoxygenase inhibitors for possible use in asthma. Agents Actions Suppl, 34: 189-99. [PMID:1793063]

14. Prasher P, Pooja, Singh P. (2014) Lead modification: amino acid appended indoles as highly effective 5-LOX inhibitors. Bioorg Med Chem, 22 (5): 1642-8. [PMID:24508141]

15. Singh P, Prasher P, Dhillon P, Bhatti R. (2015) Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents: Dual inhibition of 5-LOX and COX-2 enzymes. Eur J Med Chem, 97: 104-23. [PMID:25956953]

16. Sinha S, Doble M, Manju SL. (2018) Design, synthesis and identification of novel substituted 2-amino thiazole analogues as potential anti-inflammatory agents targeting 5-lipoxygenase. Eur J Med Chem, 158: 34-50. [PMID:30199704]

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