Target Information
Target General Information | Top | |||||
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Target ID |
T16042
(Former ID: TTDR00234)
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Target Name |
Arachidonate 15-lipoxygenase (15-LOX)
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Synonyms |
LOG15; Arachidonate omega-6 lipoxygenase; Arachidonate 12-lipoxygenase, leukocyte-type; 15-Lipoxygenase; 15-LOX-1; 12/15-lipoxygenase; 12-LOX
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Gene Name |
ALOX15
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Target Type |
Patented-recorded target
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[1] | ||||
Function |
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. 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.
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BioChemical Class |
Oxygenase
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UniProt ID | ||||||
EC Number |
EC 1.13.11.33
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Sequence |
MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV AI Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T86D6K |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 2 BioCyc Pathways | + | ||||
1 | Resolvin D biosynthesis | |||||
2 | Lipoxin biosynthesis | |||||
KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
1 | Arachidonic acid metabolism | |||||
2 | Linoleic acid metabolism | |||||
3 | Metabolic pathways | |||||
4 | Serotonergic synapse | |||||
NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
1 | IL4 Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Inflammation mediated by chemokine and cytokine signaling pathway | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Arachidonic Acid Metabolism | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | IL4-mediated signaling events | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Arachidonic acid metabolism | |||||
2 | Eicosanoid Synthesis |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | 15-Lipoxygenase inhibitors: a patent review.Expert Opin Ther Pat. 2016;26(1):65-88. | |||||
REF 2 | Inhibitors of phospholipase A2 and their therapeutic potential: an update on patents (2012-2016).Expert Opin Ther Pat. 2017 Feb;27(2):217-225. | |||||
REF 3 | Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries. Bioorg Med Chem. 2007 Nov 15;15(22):6900-8. | |||||
REF 4 | Exploring sponge-derived terpenoids for their potency and selectivity against 12-human, 15-human, and 15-soybean lipoxygenases. J Nat Prod. 2003 Feb;66(2):230-5. | |||||
REF 5 | Lipoxygenase inhibitory constituents of the fruits of noni (Morinda citrifolia) collected in Tahiti. J Nat Prod. 2007 May;70(5):859-62. | |||||
REF 6 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 7 | Probing the activity differences of simple and complex brominated aryl compounds against 15-soybean, 15-human, and 12-human lipoxygenase. J Med Chem. 2004 Jul 29;47(16):4060-5. | |||||
REF 8 | Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. J Nat Prod. 2009 Oct;72(10):1857-63. |
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