Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT12ABZ)

• DTT Name: Arachidonate 12-lipoxygenase (12-LOX)
• Synonyms: Platelet-type lipoxygenase 12; Lipoxin synthase 12-LO; LOG12; Arachidonate 12-lipoxygenase, 12S-type; 12S-lipoxygenase; 12S-LOX; 12LO; 12-lipoxygenase
• Gene Name: ALOX12
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Oxygenase
• UniProt ID: LOX12_HUMAN
• TTD ID: T35527
• EC Number: EC 1.13.11.31
• Sequence:
  MGRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLL
  QFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEGTARLPGDNA
  LDMFQKHREKELKDRQQIYCWATWKEGLPLTIAADRKDDLPPNMRFHEEKRLDFEWTLKA
  GALEMALKRVYTLLSSWNCLEDFDQIFWGQKSALAEKVRQCWQDDELFSYQFLNGANPML
  LRRSTSLPSRLVLPSGMEELQAQLEKELQNGSLFEADFILLDGIPANVIRGEKQYLAAPL
  VMLKMEPNGKLQPMVIQIQPPNPSSPTPTLFLPSDPPLAWLLAKSWVRNSDFQLHEIQYH
  LLNTHLVAEVIAVATMRCLPGLHPIFKFLIPHIRYTMEINTRARTQLISDGGIFDKAVST
  GGGGHVQLLRRAAAQLTYCSLCPPDDLADRGLLGLPGALYAHDALRLWEIIARYVEGIVH
  LFYQRDDIVKGDPELQAWCREITEVGLCQAQDRGFPVSFQSQSQLCHFLTMCVFTCTAQH
  AAINQGQLDWYAWVPNAPCTMRMPPPTTKEDVTMATVMGSLPDVRQACLQMAISWHLSRR
  QPDMVPLGHHKEKYFSGPKPKAVLNQFRTDLEKLEKEITARNEQLDWPYEYLKPSCIENS
  VTI
• Function: 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. 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.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
  Serotonergic synapse (hsa04726)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  Synthesis of Lipoxins (LX) (R-HSA-2142700)
  Synthesis of 12-eicosatetraenoic acid derivatives (R-HSA-2142712)
  Biosynthesis of DHA-derived SPMs (R-HSA-9018677)
  Biosynthesis of DPAn-6 SPMs (R-HSA-9025106)
  Biosynthesis of DPAn-3-derived maresins (R-HSA-9026290)
  Synthesis of Hepoxilins (HX) and Trioxilins (TrX) (R-HSA-2142696)
• BioCyc Pathway: MetaCyc:HS03167-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NSC-661755	DMDJT7U	N. A.	N. A.	Terminated	[1]

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-(5S,8S,10S)-20-methoxy-9,15-ene-puupehenol	DMLDQWT	Discovery agent	N.A.	Investigative	[2]
(+)-(5S,8S,10S)-20-methoxypuupehenol	DMU7BJA	Discovery agent	N.A.	Investigative	[2]
(+)-(5S,8S,9R,10S)-20-methoxypuupehenone	DMD4YPO	Discovery agent	N.A.	Investigative	[2]
(-)-7-N-methyldibromophakellin	DM396OK	Discovery agent	N.A.	Investigative	[3]
2,3,4,5-Tetrabromo-6-(2,4-dibromo-phenoxy)-phenol	DMK4LTB	Discovery agent	N.A.	Investigative	[4]
3,4,6-Tribromo-2-(2,4-dibromo-phenoxy)-phenol	DMO34LJ	Discovery agent	N.A.	Investigative	[4]
CHLOROPUUPEHENONE	DM8B0VZ	Discovery agent	N.A.	Investigative	[2]
Dimethylnordihydroguarierate acid	DMG3WTE	Discovery agent	N.A.	Investigative	[2]
DYSIDENIN	DMIZQTX	Discovery agent	N.A.	Investigative	[1]
Isojaspic acid	DMHTBDN	Discovery agent	N.A.	Investigative	[5]
Jaspic acid	DMOF0TB	Discovery agent	N.A.	Investigative	[2]
MANGOSTIN	DMYQGDV	Discovery agent	N.A.	Investigative	[1]
NEODYSIDENIN	DM5EWIK	Discovery agent	N.A.	Investigative	[1]
NSC-125034	DM3NQDW	Discovery agent	N.A.	Investigative	[1]
NSC-172033	DM9QW8N	Discovery agent	N.A.	Investigative	[1]
NSC-292213	DMNUSKT	Discovery agent	N.A.	Investigative	[1]
Polybrominated diphenyl ether derivative	DMG7K84	Discovery agent	N.A.	Investigative	[4]
PUUPEHEDIONE	DMF28IU	Discovery agent	N.A.	Investigative	[5]
PUUPEHENONE	DMF3BCK	Discovery agent	N.A.	Investigative	[2]

References

• [1] 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.
• [2] 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.
• [3] An analysis of phakellin and oroidin structures stimulated by further study of an Agelas sponge. J Nat Prod. 2004 Aug;67(8):1256-61.
• [4] 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.
• [5] Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. J Nat Prod. 2009 Oct;72(10):1857-63.