5-LOX | Lipoxygenases | IUPHAR/BPS Guide to PHARMACOLOGY

5-LOX

Target id: 1385

Nomenclature: 5-LOX

Family: Lipoxygenases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     5-LOX has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 674 10q11.2 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
ALOX5 | 5-lipoxygenase | 5-LO | arachidonate 5-lipoxygenase
Database Links
BRENDA
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.13.11.34 Arachidonic acid + O2 = LTA4 + H2O
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
arachidonic acid Hs - -
Endogenous inhibitor
Protein kinase A-mediated phosphorylation  [8]

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
5-LOX activating protein {Sp: Human} Hs Activation - -
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CJ13610 Hs Inhibition 7.2 pIC50 5
pIC50 7.2 (IC50 7x10-8 M) [5]
PF-04191834 Hs Inhibition 6.6 pIC50 9
pIC50 6.6 (IC50 2.29x10-7 M) [9]
zileuton Hs Inhibition 5.8 – 6.5 pIC50 2,12,14
pIC50 6.5 (IC50 3x10-7 M) [12]
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) [14]
Description: Inhibition of purified recombinant human 5-LOX in a cell-free assay.
5-LOX inhibitor 2m [PMID: 30199704] Hs Inhibition 6.1 pIC50 14
pIC50 6.1 (IC50 9x10-7 M) [14]
Description: In vitro biochemical inhibitory activity.
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 [14]. 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 [1,3-4,6-7,10-11,13].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0043312 neutrophil degranulation TAS
click arrow to show/hide IEA associations
GO:0002540 leukotriene production involved in inflammatory response IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Clinically-Relevant Mutations and Pathophysiology
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. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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 [Epub ahead of print]. [PMID:29883727]

12. 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]

13. 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]

14. 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 [Epub ahead of print]. [PMID:30199704]

How to cite this page

Lipoxygenases: 5-LOX. Last modified on 11/09/2018. Accessed on 25/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1385.