Target General Infomation
Target ID
T16042
Former ID
TTDR00234
Target Name
Arachidonate 15-lipoxygenase
Gene Name
ALOX15
Synonyms
15-LOX; 15-Lipoxygenase; Arachidonate omega-6 lipoxygenase; ALOX15
Target Type
Discontinued
Function
Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid into 12- hydroperoxyeicosatetraenoic acid/12-HPETE and 15- hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass.
BioChemical Class
Oxidoreductases acting on single donors
Target Validation
T16042
UniProt ID
EC Number
EC 1.13.11.33
Sequence
MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP
QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK
GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV
LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL
VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH
LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST
GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS
LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH
ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ
PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV
AI
Structure
2ABT
Drugs and Mode of Action
Drug(s) NSC-661755 Drug Info Terminated Discovery agent [545654]
Inhibitor (+)-(5S,8S,10S)-20-methoxy-9,15-ene-puupehenol Drug Info [526556]
(+)-(5S,8S,10S)-20-methoxypuupehenol Drug Info [526556]
(+)-(5S,8S,9R,10S)-20-methoxypuupehenone Drug Info [526556]
(+)-3,3'-bisdemethyltanegool Drug Info [528750]
(-)-3,3'-bisdemethylpinoresinol Drug Info [528750]
(-)-pinoresinol Drug Info [528750]
(2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID Drug Info [551374]
2,3,4,5-Tetrabromo-6-(2,4-dibromo-phenoxy)-phenol Drug Info [527145]
3,4,6-Tribromo-2-(2,4-dibromo-phenoxy)-phenol Drug Info [527145]
3,4-Dibromo-2-(5-bromo-2-hydroxy-phenoxy)-phenol Drug Info [527145]
3,6,8-Tribromo-dibenzo[1,4]dioxin-1-ol Drug Info [527145]
Benzothiopyranoindole Drug Info [534839]
CHLOROPUUPEHENONE Drug Info [526556]
Dimethylnordihydroguarierate acid Drug Info [526556]
DYSIDENIN Drug Info [529029]
Halisulfate 1 Drug Info [526556]
Hydrohalisulfate 1 Drug Info [526556]
IGERNELLIN Drug Info [526556]
Isojaspic acid Drug Info [530468]
ISOSCOPOLETIN Drug Info [528750]
JASPAQUINOL Drug Info [530468]
Jaspic acid Drug Info [526556]
KAEMPFEROL Drug Info [528750]
Nonsteroidal anti-inflammatory drugs (NSAIDs) Drug Info [535013]
NSC-172033 Drug Info [529029]
NSC-30552 Drug Info [529029]
NSC-661755 Drug Info [529029]
Polybrominated diphenyl ether derivative Drug Info [527145]
PUUPEHEDIONE Drug Info [530468]
PUUPEHENONE Drug Info [530468]
SCOPOLETIN Drug Info [528750]
SPONGIADIOXIN A Drug Info [527145]
Subersic acid Drug Info [526556]
Pathways
BioCyc Pathway Resolvin D biosynthesis
Lipoxin biosynthesis
KEGG Pathway Arachidonic acid metabolism
Linoleic acid metabolism
Metabolic pathways
Serotonergic synapse
NetPath Pathway IL4 Signaling Pathway
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Pathway Interaction Database IL4-mediated signaling events
PathWhiz Pathway Arachidonic Acid Metabolism
WikiPathways Arachidonic acid metabolism
Eicosanoid Synthesis
References
Ref 545654Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004041)
Ref 526556J Nat Prod. 2003 Feb;66(2):230-5.Exploring sponge-derived terpenoids for their potency and selectivity against 12-human, 15-human, and 15-soybean lipoxygenases.
Ref 527145J Med Chem. 2004 Jul 29;47(16):4060-5.Probing the activity differences of simple and complex brominated aryl compounds against 15-soybean, 15-human, and 12-human lipoxygenase.
Ref 528750J Nat Prod. 2007 May;70(5):859-62. Epub 2007 Mar 23.Lipoxygenase inhibitory constituents of the fruits of noni (Morinda citrifolia) collected in Tahiti.
Ref 529029Bioorg Med Chem. 2007 Nov 15;15(22):6900-8. Epub 2007 Aug 22.Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries.
Ref 530468J Nat Prod. 2009 Oct;72(10):1857-63.Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes.
Ref 53483915-Lipoxygenase and its inhibition: a novel therapeutic target for vascular disease. Curr Pharm Des. 1999 Jan;5(1):11-20.
Ref 53501315-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells. J Natl Cancer Inst. 2000 Jul 19;92(14):1136-42.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

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