Target Information

Target General Infomation
Target ID
T35527
Former ID
TTDR00239
Target Name
Arachidonate 12-lipoxygenase, 12S-type
Gene Name
ALOX12
Synonyms
12-LOX; 12-lipoxygenase; Platelet-type lipoxygenase 12; ALOX12
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. Mainly converts arachidonic acid to (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation.
BioChemical Class
Oxidoreductases acting on single donors
Target Validation
T35527
UniProt ID
P18054
EC Number
EC 1.13.11.31
Sequence
MGRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLL
QFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEGTARLPGDNA
LDMFQKHREKELKDRQQIYCWATWKEGLPLTIAADRKDDLPPNMRFHEEKRLDFEWTLKA
GALEMALKRVYTLLSSWNCLEDFDQIFWGQKSALAEKVRQCWQDDELFSYQFLNGANPML
LRRSTSLPSRLVLPSGMEELQAQLEKELQNGSLFEADFILLDGIPANVIRGEKQYLAAPL
VMLKMEPNGKLQPMVIQIQPPNPSSPTPTLFLPSDPPLAWLLAKSWVRNSDFQLHEIQYH
LLNTHLVAEVIAVATMRCLPGLHPIFKFLIPHIRYTMEINTRARTQLISDGGIFDKAVST
GGGGHVQLLRRAAAQLTYCSLCPPDDLADRGLLGLPGALYAHDALRLWEIIARYVEGIVH
LFYQRDDIVKGDPELQAWCREITEVGLCQAQDRGFPVSFQSQSQLCHFLTMCVFTCTAQH
AAINQGQLDWYAWVPNAPCTMRMPPPTTKEDVTMATVMGSLPDVRQACLQMAISWHLSRR
QPDMVPLGHHKEKYFSGPKPKAVLNQFRTDLEKLEKEITARNEQLDWPYEYLKPSCIENS
VTI
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]
(-)-7-N-methyldibromophakellin Drug Info [527187]
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]
CHLOROPUUPEHENONE Drug Info [526556]
Dimethylnordihydroguarierate acid Drug Info [526556]
DYSIDENIN Drug Info [529029]
Isojaspic acid Drug Info [530468]
Jaspic acid Drug Info [526556]
NEODYSIDENIN Drug Info [529029]
NSC-125034 Drug Info [529029]
NSC-172033 Drug Info [529029]
NSC-292213 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 [526556]
Pathways
BioCyc Pathway Lipoxin biosynthesis
KEGG Pathway Arachidonic acid metabolism
Metabolic pathways
Serotonergic synapse
Inflammatory mediator regulation of TRP channels
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
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 527187J Nat Prod. 2004 Aug;67(8):1256-61.An analysis of phakellin and oroidin structures stimulated by further study of an Agelas sponge.
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.

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