Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN9T81)

• DTT Name: Arachidonate 15-lipoxygenase (15-LOX)
• Synonyms: LOG15; Arachidonate omega-6 lipoxygenase; Arachidonate 12-lipoxygenase, leukocyte-type; 15-Lipoxygenase; 15-LOX-1; 12/15-lipoxygenase; 12-LOX
• Gene Name: ALOX15
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Oxygenase
• UniProt ID: LOX15_HUMAN
• TTD ID: T16042
• EC Number: EC 1.13.11.33
• Sequence:
  MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
  LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP
  QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK
  GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV
  LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL
  VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH
  LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST
  GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS
  LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH
  ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ
  PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV
  AI
• 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.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Linoleic acid metabolism (hsa00591)
  Metabolic pathways (hsa01100)
  Serotonergic synapse (hsa04726)
• Reactome Pathway:
  Synthesis of 12-eicosatetraenoic acid derivatives (R-HSA-2142712)
  Synthesis of 15-eicosatetraenoic acid derivatives (R-HSA-2142770)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Biosynthesis of DHA-derived SPMs (R-HSA-9018677)
  Biosynthesis of protectins (R-HSA-9018681)
  Biosynthesis of E-series 18(S)-resolvins (R-HSA-9018896)
  Biosynthesis of E-series 18(R)-resolvins (R-HSA-9023661)
  Biosynthesis of DPAn-6 SPMs (R-HSA-9025106)
  Biosynthesis of DPAn-3-derived protectins and resolvins (R-HSA-9026286)
  Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691)
• BioCyc Pathway: MetaCyc:HS08621-MON

Molecular Interaction Atlas (MIA) of This DTT

8 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imidazole derivative 10	DMI7W3K	N. A.	N. A.	Patented	[1]
Imidazole derivative 11	DMTJ0DP	N. A.	N. A.	Patented	[1]
Indole and benzimidazole derivative 1	DMS0169	N. A.	N. A.	Patented	[1]
Indolizine derivative 1	DM4GZBI	N. A.	N. A.	Patented	[2]
Isothiazolone derivative 1	DMHAJCM	N. A.	N. A.	Patented	[1]
PMID26560362-Compound-90	DM9V13U	N. A.	N. A.	Patented	[1]
Tri-substituted benzene derivative 1	DMEQ3RD	N. A.	N. A.	Patented	[1]
Triazole derivative 3	DMZR0TH	N. A.	N. A.	Patented	[1]

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	[3]

30 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	[4]
(+)-(5S,8S,10S)-20-methoxypuupehenol	DMU7BJA	Discovery agent	N.A.	Investigative	[4]
(+)-(5S,8S,9R,10S)-20-methoxypuupehenone	DMD4YPO	Discovery agent	N.A.	Investigative	[4]
(+)-3,3'-bisdemethyltanegool	DMNUWVB	Discovery agent	N.A.	Investigative	[5]
(-)-3,3'-bisdemethylpinoresinol	DMGC7F5	Discovery agent	N.A.	Investigative	[5]
(-)-pinoresinol	DM4INSG	Discovery agent	N.A.	Investigative	[5]
(2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID	DMKWRFA	Discovery agent	N.A.	Investigative	[6]
2,3,4,5-Tetrabromo-6-(2,4-dibromo-phenoxy)-phenol	DMK4LTB	Discovery agent	N.A.	Investigative	[7]
3,4,6-Tribromo-2-(2,4-dibromo-phenoxy)-phenol	DMO34LJ	Discovery agent	N.A.	Investigative	[7]
3,4-Dibromo-2-(5-bromo-2-hydroxy-phenoxy)-phenol	DMXQVRD	Discovery agent	N.A.	Investigative	[7]
3,6,8-Tribromo-dibenzo[1,4]dioxin-1-ol	DMM632N	Discovery agent	N.A.	Investigative	[7]
CHLOROPUUPEHENONE	DM8B0VZ	Discovery agent	N.A.	Investigative	[4]
Dimethylnordihydroguarierate acid	DMG3WTE	Discovery agent	N.A.	Investigative	[4]
DYSIDENIN	DMIZQTX	Discovery agent	N.A.	Investigative	[3]
Halisulfate 1	DMJB87Q	Discovery agent	N.A.	Investigative	[4]
Hydrohalisulfate 1	DM0HQF6	Discovery agent	N.A.	Investigative	[4]
IGERNELLIN	DMFMY1L	Discovery agent	N.A.	Investigative	[4]
Isojaspic acid	DMHTBDN	Discovery agent	N.A.	Investigative	[8]
ISOSCOPOLETIN	DMNM2SQ	Discovery agent	N.A.	Investigative	[5]
JASPAQUINOL	DMJAEMT	Discovery agent	N.A.	Investigative	[8]
Jaspic acid	DMOF0TB	Discovery agent	N.A.	Investigative	[4]
KAEMPFEROL	DMHEMUB	Discovery agent	N.A.	Investigative	[5]
MANGOSTIN	DMYQGDV	Discovery agent	N.A.	Investigative	[3]
NSC-172033	DM9QW8N	Discovery agent	N.A.	Investigative	[3]
Polybrominated diphenyl ether derivative	DMG7K84	Discovery agent	N.A.	Investigative	[7]
PUUPEHEDIONE	DMF28IU	Discovery agent	N.A.	Investigative	[8]
PUUPEHENONE	DMF3BCK	Discovery agent	N.A.	Investigative	[8]
SCOPOLETIN	DM645FP	Discovery agent	N.A.	Investigative	[5]
SPONGIADIOXIN A	DM0GJVS	Discovery agent	N.A.	Investigative	[7]
Subersic acid	DM8BLXT	Discovery agent	N.A.	Investigative	[4]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Arachidonate 15-lipoxygenase (ALOX15) DME Info
• Gene Name: ALOX15

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arachidonic Acid	DMUOQZD	Discovery agent	N.A.	Investigative	[9]

References

• [1] 15-Lipoxygenase inhibitors: a patent review.Expert Opin Ther Pat. 2016;26(1):65-88.
• [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.
• [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.
• [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.
• [5] Lipoxygenase inhibitory constituents of the fruits of noni (Morinda citrifolia) collected in Tahiti. J Nat Prod. 2007 May;70(5):859-62.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [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.
• [8] Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. J Nat Prod. 2009 Oct;72(10):1857-63.
• [9] Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse mesenteric arteries and hearts. Prostaglandins Other Lipid Mediat. 2013 Oct;106:8-15.