ALOX15

Summary

ALOX15 (arachidonate 15-lipoxygenase, HGNC:433) is a protein-coding gene on chromosome 17p13.2, encoding Polyunsaturated fatty acid lipoxygenase ALOX15 (P16050). 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.

This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome.

Source: NCBI Gene 246 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pregnancy loss, recurrent, susceptibility (Limited, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 129 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 174 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001140

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:433
Approved symbol	ALOX15
Name	arachidonate 15-lipoxygenase
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	15-LOX-1
Ensembl gene	ENSG00000161905
Ensembl biotype	protein_coding
OMIM	152392
Entrez	246

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000293761, ENST00000570836, ENST00000572265, ENST00000573740, ENST00000574640, ENST00000576572

RefSeq mRNA: 1 — MANE Select: NM_001140 NM_001140

CCDS: CCDS11049

Canonical transcript exons

ENST00000293761 — 14 exons

Exon	Start	End
ENSE00001061261	4637115	4637258
ENSE00001061262	4635759	4635968
ENSE00001061264	4633414	4633500
ENSE00001061266	4631889	4632056
ENSE00001061267	4633146	4633315
ENSE00001061269	4638581	4638684
ENSE00001061270	4632861	4632982
ENSE00001195427	4641517	4641678
ENSE00001651707	4632181	4632281
ENSE00002641038	4630919	4631779
ENSE00003466741	4638850	4638972
ENSE00003507495	4639430	4639631
ENSE00003522867	4639051	4639132
ENSE00003534598	4638217	4638377

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 98.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6751 / max 572.0559, expressed in 125 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163926	1.6496	123
163925	0.0209	7
163927	0.0047	2

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	98.81	gold quality
bronchial epithelial cell	CL:0002328	97.11	gold quality
epithelium of bronchus	UBERON:0002031	95.90	gold quality
bronchus	UBERON:0002185	95.17	gold quality
nasal cavity epithelium	UBERON:0005384	94.89	gold quality
oocyte	CL:0000023	91.50	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.89	gold quality
secondary oocyte	CL:0000655	87.08	gold quality
nasal cavity mucosa	UBERON:0001826	86.79	gold quality
endometrium epithelium	UBERON:0004811	80.36	gold quality
omental fat pad	UBERON:0010414	77.95	gold quality
peritoneum	UBERON:0002358	77.85	gold quality
right uterine tube	UBERON:0001302	77.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.92	gold quality
trachea	UBERON:0003126	75.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.17	gold quality
right lung	UBERON:0002167	71.40	gold quality
parietal pleura	UBERON:0002400	70.32	gold quality
adenohypophysis	UBERON:0002196	67.42	gold quality
olfactory bulb	UBERON:0002264	67.19	gold quality
pericardium	UBERON:0002407	64.82	silver quality
pleura	UBERON:0000977	64.65	gold quality
pituitary gland	UBERON:0000007	64.48	gold quality
blood	UBERON:0000178	63.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	60.81	gold quality
lymph node	UBERON:0000029	60.14	gold quality
vermiform appendix	UBERON:0001154	59.89	gold quality
trabecular bone tissue	UBERON:0002483	59.49	silver quality
bone marrow	UBERON:0002371	59.39	silver quality
lower esophagus mucosa	UBERON:0035834	58.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	3.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREBBP, DNMT1, EP300, GATA6, HDAC1, MBD2, MTA1, SPI1, STAT6, TCF3, TP53, XRCC5

miRNA regulators (miRDB)

47 targeting ALOX15, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-3125	99.14	68.49	2269

Literature-anchored findings (GeneRIF, showing 40)

• Kelavkar and Badr (1999) stated that the ALOX15 gene maps to 17p13.3 in close proximity to the tumor-suppressor gene TP53 and stated that the ALOX15 gene product is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. (PMID:10200270)
• 15-LO-1 expression was significantly high in prostate adenocarcinoma and seen in secretory cells of peripheral zone glands, prostatic ducts and seminal vesicles, but not in the basal cell layer or stroma. (PMID:11023533)
• metabolizes 2-arachidonylglycerol, an endo cannabinoid, to a peroxisome proliferator-activated receptor alpha agonist (PMID:11956198)
• This article emphasizes the key role of 15-Lipoxygenase-1 in prostate, colorectal, and breast cancers. (PMID:12084190)
• This enzyme is overexpressed in prostatic adenocarcinoma. (PMID:12664577)
• This enzyme is induced when Ku antigen is the transcripion factor in human cells. (PMID:12664628)
• Results provide evidence that interleukin-13 induces p38 MAP kinase phosphorylation and activation, which regulates Stat1 and Stat3 serine 727 phosphorylation. (PMID:12748293)
• human breast tumours aber;antly express decreased level of ALOX15. Lobular carcinomas had a lower level of ALOX15 than ductal carcinomas; the lowest level of ALOX15 was seen in TNM3 and TNM4 tumours and from patients who died of breast cancer. (PMID:12907138)
• In athymic nude mice, transplantable tumors derived from 15-LO-1 HCT-116 cells were smaller than tumors derived from vector HCT-116 cells (PMID:14643174)
• PKCdelta plays an important role in regulating 15-lipoxygenase expression in human monocytes and subsequently modulates the inflammatory responses mediated by 15-LO products (PMID:14757756)
• 12/15-lipoxygenase is increased in Alzheimer’s disease and has a possible role in brain oxidative stress (PMID:15111312)
• Demethylation of the 15-LO promoter is a prerequisite for the gene transactivation, which contributes to tissue- and cell-type-specific regulation of 15-LO expression. (PMID:15194425)
• Studies using transgenic mice overexpressing human 15-lipoxygenase suggest a role for 15-LO in the natural selection of thymocytes. (PMID:15459485)
• These findings suggest that the ALOX15 gene is one of the genetic determinants of bone mineral density in postmenopausal women. Accordingly, this polymorphism could be useful as a genetic marker for predicting the risk of osteoporosis. (PMID:15838625)
• The suppressive activity of antiproliferative myeloid suppressor cells (MSC) in the peritoneal cavity of mice infected with Taenia crassiceps depends on a switch from nitric oxide- to 12-15-lipoxygenase-dependent alternative activation MSC phenotype. (PMID:15879104)
• 15-LOX-1 gene expression is significantly reduced in both human colorectal adenomas and carcinomas and is associated with decreased survival. Down regulation of 15-LOX-1 is an early event in the adenoma to carcinoma sequence. (PMID:15912043)
• Strong overexpression of 15-lipoxygenase1 was paralleled by downregulation of CD4 and CXCR4. (PMID:15967444)
• 15-LO-1 is related to the differentiation of human nasal epithelium, and that it may mediate the mucociliary differentiation of human nasal epithelium. (PMID:15996861)
• ALOX15 generation of 15S-hydroxyeicosatetraenoic acid activates specific growth factor receptor-related signaling pathways, thereby initiating signal transduction events leading to increased cell adhesion to extracellular matrix in breast carcinoma cells (PMID:16000313)
• Overexpression of 15-lipoxygenase-1 induces growth arrest through phosphorylation of p53 in human colorectal cancer cells (PMID:16179498)
• The c.-292 T allele in the ALOX15 promoter generates a novel binding site for the transcription factor SPI1 that results in higher transcription of the gene in macrophages. (PMID:16320347)
• Down-regulation of 15-Lipoxygenase-1 is associated with colorectal adenomas (PMID:16357157)
• Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer (PMID:16556493)
• Results describe the shared stabilization functions of pyrimidine-rich determinants in the erythroid 15-lipoxygenase and alpha-globin mRNAs. (PMID:16847316)
• Results suggest that aberrant 15-lipoxygenase-1 overexpression in normal prostate can trigger events leading to prostate epithelial and stromal cell proliferation. (PMID:16997127)
• 12/15-lipoxygenase expression suppresses the growth of human Bcr-Abl+ leukemia K562 cells. (PMID:17043146)
• proposed a possible reaction pathway in 15-lipoxygenase reactions at lower oxygen content (PMID:17227895)
• The data presented link the stimulation of ERK-cPLA(2)-15-LO pathway by oxidized LDL to the prooxidant mechanism of the lipoprotein complex. (PMID:17344094)
• the c.-292C>T polymorphism was associated with higher enzyme activity in heterozygous carriers; this polymorphism also showed a tendency to be protective against atherosclerosis (PMID:17439326)
• there is no association between polymorphism in ALOX15 and bone mineral density phenotypes, but genetic variation in ALOX12 seems to play a role in determining bone structure in Caucasian women (PMID:17520163)
• variant alleles of rs2619112 and rs916055 and their haplotypes of ALOX15 are associated with high bone mineral density(BMD) in pre-menopausal women but low BMD in post-menopausal women (PMID:17652958)
• Results report that interleukin-4 (IL-4) induced the expression of 15-LO-1 in human cord blood derived mast cells (CBMC). (PMID:17662651)
• The switching of linoleic acid metabolism by reversal of the expression of 15LOX-1 and COX-2 is associated with acquisition of malignant potential in colonic neoplasia. (PMID:17711445)
• A coding single nucleotide polymorphism in ALOX15 (T560M) results in a near null variant of human 12/15-LOX and this variant does not protect against coronary artery disease (PMID:17959182)
• expression of endogenous rabbit peroxisome proliferator-activating receptor and VEGFR2 were significantly increased in the growth factor-transduced muscles, but these inductions were efficiently prevented by 15-LO-1. (PMID:17991885)
• increased expression of 15-LOX-2 induced by hypoxia may participate in T cell recruitment in diseases such as atherosclerosis (PMID:18067895)
• 15-lipoxygenase-2 mRNA is strongly augmented during ovarian carcinogenesis and that the enzyme may constitute a suitable candidate as a tumor marker. (PMID:18090132)
• Increased expression of 15-lipoxygenase-1 increases acetylcholine relaxation in arteries and hypotensive responses in rabbits because of increased hydroxy-epoxyeicosatrienoic acid and trihydroxyeicosatrienoic acid synthesis. (PMID:18180398)
• These results demonstrate a novel mechanism of parathyroid hormone-induced human bone cell proliferation operating through 12- and 15-lipoxygenase enzymes. (PMID:18187376)
• DNMT-1 has a direct suppressive role in 15-LOX-1 transcriptional silencing that is independent of 15-LOX-1 promoter DNA methylation (PMID:18198215)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Alox15	ENSMUSG00000018924
rattus_norvegicus	Alox15	ENSRNOG00000019183

Paralogs (5): ALOX5 (ENSG00000012779), ALOX12 (ENSG00000108839), ALOXE3 (ENSG00000179148), ALOX12B (ENSG00000179477), ALOX15B (ENSG00000179593)

Protein

Protein identifiers

Polyunsaturated fatty acid lipoxygenase ALOX15 — P16050 (reviewed: P16050)

Alternative names: 12/15-lipoxygenase, Arachidonate 12-lipoxygenase, leukocyte-type, Arachidonate 15-lipoxygenase, Arachidonate omega-6 lipoxygenase, Hepoxilin A3 synthase Alox15, Linoleate 13S-lipoxygenase

All UniProt accessions (1): P16050

UniProt curated annotations — full annotation on UniProt →

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. It inserts peroxyl groups at C12 or C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-hydroperoxyeicosatetraenoate/12-HPETE and 15-hydroperoxyeicosatetraenoate/15-HPETE. It may then act on 12-HPETE to produce hepoxilins, which may show pro-inflammatory properties. Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE. May participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets. Can convert epoxy fatty acids to hydroperoxy-epoxides derivatives followed by an intramolecular nucleophilic substitution leading to the formation of monocyclic endoperoxides. Plays an important role during the maintenance of self-tolerance by peroxidizing membrane-bound phosphatidylethanolamine which can then signal the sorting process for clearance of apoptotic cells during inflammation and prevent an autoimmune response. In addition to its role in the immune and inflammatory responses, this enzyme may play a role in epithelial wound healing in the cornea through production of lipoxin A4 (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1; 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory and neuroprotective properties. Furthermore, it may regulate actin polymerization which is crucial for several biological processes such as the phagocytosis of apoptotic cells. It is also implicated in the generation of endogenous ligands for peroxisome proliferator activated receptor (PPAR-gamma), hence modulating macrophage development and function. It may also exert a negative effect on skeletal development by regulating bone mass through this pathway. As well as participates in ER stress and downstream inflammation in adipocytes, pancreatic islets, and liver. Finally, it is also involved in the cellular response to IL13/interleukin-13.

Subunit / interactions. Interacts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade.

Subcellular location. Cytoplasm. Cytosol. Cell membrane. Lipid droplet.

Tissue specificity. Detected in monocytes and eosinophils (at protein level). Expressed in airway epithelial cells.

Disease relevance. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Met at position 560 may confer interindividual susceptibility to coronary artery disease (CAD).

Activity regulation. Activity is increased by binding phosphatidylinositol phosphates, especially phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate. Inactivated at 37 degrees Celsius by (13S)-hydroperoxy-(9Z,11E)-octadecadienoate.

Cofactor. Binds 1 Fe cation per subunit.

Domain organisation. The PLAT domain can bind calcium ions; this promotes association with membranes.

Induction. Up-regulated by UV-irradiation.

Pathway. Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.

Similarity. Belongs to the lipoxygenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P16050-1	1	yes
P16050-2	2

RefSeq proteins (1): NP_001131* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000907	LipOase	Family
IPR001024	PLAT/LH2_dom	Domain
IPR001885	LipOase_mml	Family
IPR013819	LipOase_C	Domain
IPR020833	LipOase_Fe_BS	Binding_site
IPR020834	LipOase_CS	Conserved_site
IPR036226	LipOase_C_sf	Homologous_superfamily
IPR036392	PLAT/LH2_dom_sf	Homologous_superfamily
IPR042062	PLAT_LOX_verte	Domain

Pfam: PF00305, PF01477

Enzyme classification (BRENDA):

• EC 1.13.11.31 — arachidonate 12-lipoxygenase (BRENDA: 25 organisms, 141 substrates, 194 inhibitors, 60 Km, 34 kcat entries)
• EC 1.13.11.33 — arachidonate 15-lipoxygenase (BRENDA: 27 organisms, 136 substrates, 653 inhibitors, 65 Km, 54 kcat entries)

Substrate kinetics (BRENDA)

32 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ARACHIDONIC ACID	0.0025–1.1	15
ARACHIDONIC ACID	0.004–0.08	14
O2	0.0052–4.2	10
ARACHIDONATE	0.0009–0.232	8
LINOLEIC ACID	0.0125–0.0312	8
O2	0.0052–7	8
ARACHIDONATE	0.0009–0.013	8
LINOLEIC ACID	0.003–0.0772	7
5,8,11,14,17-EICOSAPENTAENOIC ACID	0.003–0.427	4
5S-HYDROPEROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC AC	0.0017–0.057	3
5S-HYDROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC ACID	0.0017–0.029	3
4Z,7Z,10Z,12E,16Z,19Z-DOCOSAHEXAENOIC ACID	0.0009–0.0067	2
5S-HYDROPEROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC AC	0.0017–0.0078	2
5S-HYDROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC ACID	0.0017–0.0049	2
8,11,14-EICOSATRIENOIC ACID	0.0035–0.079	2

Catalyzed reactions (Rhea), 12 shown:

• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate (RHEA:10428)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (RHEA:16869)
• (9Z,12Z)-octadecadienoate + O2 = (13S)-hydroperoxy-(9Z,11E)-octadecadienoate (RHEA:22780)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate (RHEA:41332)
• (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = (14S,15S)-epoxy-(5Z,8Z,10E,12E)-eicosatetraenoate + H2O (RHEA:50140)
• (15R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O (RHEA:50152)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-taurine (RHEA:50156)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-taurine (RHEA:50160)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-glycine (RHEA:50168)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-L-alanine + O2 = N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-alanine (RHEA:50172)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 = N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-gamma-aminobutanoate (RHEA:50176)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 = N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-gamma-aminobutanoate (RHEA:50180)

UniProt features (23 total): sequence variant 11, binding site 5, domain 2, initiator methionine 1, chain 1, mutagenesis site 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16050-F1	95.46	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 360; 365; 540; 544; 662

Mutagenesis-validated functional residues (1):

Position	Phenotype
418	catalyzes 15- and 12-lipoxygenation.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142712	Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-2142770	Synthesis of 15-eicosatetraenoic acid derivatives
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9018677	Biosynthesis of DHA-derived SPMs
R-HSA-9018681	Biosynthesis of protectins
R-HSA-9018896	Biosynthesis of E-series 18(S)-resolvins
R-HSA-9023661	Biosynthesis of E-series 18(R)-resolvins
R-HSA-9025106	Biosynthesis of DPAn-6 SPMs
R-HSA-9026286	Biosynthesis of DPAn-3-derived protectins and resolvins
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-168256	Immune System
R-HSA-2142753	Arachidonate metabolism
R-HSA-449147	Signaling by Interleukins
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9018678	Biosynthesis of specialized proresolving mediators (SPMs)
R-HSA-9018679	Biosynthesis of EPA-derived SPMs
R-HSA-9018683	Biosynthesis of DPA-derived SPMs
R-HSA-9025094	Biosynthesis of DPAn-3 SPMs

MSigDB gene sets: 311 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (26): ossification (GO:0001503), negative regulation of adaptive immune response (GO:0002820), lipid metabolic process (GO:0006629), phosphatidylethanolamine biosynthetic process (GO:0006646), inflammatory response (GO:0006954), positive regulation of cell-substrate adhesion (GO:0010811), arachidonate metabolic process (GO:0019369), lipoxygenase pathway (GO:0019372), fatty acid oxidation (GO:0019395), bone mineralization (GO:0030282), positive regulation of actin filament polymerization (GO:0030838), lipid oxidation (GO:0034440), response to endoplasmic reticulum stress (GO:0034976), regulation of peroxisome proliferator activated receptor signaling pathway (GO:0035358), cellular response to interleukin-13 (GO:0035963), wound healing (GO:0042060), long-chain fatty acid biosynthetic process (GO:0042759), apoptotic cell clearance (GO:0043277), linoleic acid metabolic process (GO:0043651), regulation of inflammatory response (GO:0050727), hepoxilin biosynthetic process (GO:0051122), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to calcium ion (GO:0071277), regulation of engulfment of apoptotic cell (GO:1901074), lipoxin A4 biosynthetic process (GO:2001303), fatty acid metabolic process (GO:0006631)

GO Molecular Function (11): arachidonate 12(S)-lipoxygenase activity (GO:0004052), iron ion binding (GO:0005506), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), linoleate 13S-lipoxygenase activity (GO:0016165), arachidonate 15-lipoxygenase activity (GO:0050473), protein binding (GO:0005515), lipid binding (GO:0008289), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (6): lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Arachidonate metabolism	3
Biosynthesis of specialized proresolving mediators (SPMs)	3
Biosynthesis of EPA-derived SPMs	2
Metabolism of lipids	2
Signaling by Interleukins	1
Biosynthesis of DHA-derived SPMs	1
Biosynthesis of DPA-derived SPMs	1
Biosynthesis of DPAn-3 SPMs	1
Immune System	1
Fatty acid metabolism	1
Cytokine Signaling in Immune system	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
long-chain fatty acid metabolic process	3
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	3
cellular anatomical structure	3
icosanoid metabolic process	2
unsaturated fatty acid metabolic process	2
olefinic compound metabolic process	2
fatty acid metabolic process	2
binding	2
multicellular organismal process	1
adaptive immune response	1
regulation of adaptive immune response	1
negative regulation of immune response	1
primary metabolic process	1
phosphatidylethanolamine metabolic process	1
glycerophospholipid biosynthetic process	1
defense response	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
lipid oxidation	1
ossification	1
biomineral tissue development	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
lipid modification	1
cellular response to stress	1
peroxisome proliferator activated receptor signaling pathway	1
regulation of intracellular signal transduction	1
response to interleukin-13	1
cellular response to cytokine stimulus	1
response to wounding	1
tissue regeneration	1
fatty acid biosynthetic process	1
phagocytosis	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1

Protein interactions and networks

STRING

1727 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALOX15	PEBP1	P30086	984
ALOX15	LOX	P28300	852
ALOX15	GPR32	O75388	720
ALOX15	GPX4	P36969	665
ALOX15	PTGS2	P35354	629
ALOX15	ALOX5AP	P20292	611
ALOX15	PTGS1	P23219	608
ALOX15	ACSL4	O60488	600
ALOX15	LPCAT3	Q6P1A2	594
ALOX15	LTA4H	P09960	592
ALOX15	PLA2G4A	P47712	535
ALOX15	PPARG	P37231	526
ALOX15	LTB4R	Q15722	523
ALOX15	PTEN	P60484	515
ALOX15	FPR2	P25090	510

IntAct

14 interactions, top by confidence:

A	B	Type	Score
PEBP1	RAF1	psi-mi:“MI:0914”(association)	0.760
ALOX15	TIMM29	psi-mi:“MI:0915”(physical association)	0.560
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
PEBP1	ALOX15	psi-mi:“MI:0915”(physical association)	0.500
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
ALOX15	DCAF10	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): ALOX15 (Affinity Capture-MS), PRKDC (Affinity Capture-Western), ALOX15 (Affinity Capture-Western), ALOX15 (Affinity Capture-Western), PEBP1 (Affinity Capture-Western), ALOX15 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), ALOX15 (Phenotypic Suppression), DCAF10 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), ALOX15 (Affinity Capture-MS), ALOX15 (Affinity Capture-MS), ALOX15 (Affinity Capture-MS), ALOX15 (Affinity Capture-MS), ALOX15 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A6H603, D3ZBP4, D3ZKX9, D3ZQF9, F1LQ70, O00329, O00411, O15296, O35936, O43548, O70582, O75342, O95932, P09917, P0C869, P0C871, P12527, P12530, P16050, P16452, P16469, P18054, P27479, P39654, P39655, P48999, P49222, P51399, P52630, P55249, Q02759, Q149M9, Q2KMM4, Q2TB18, Q4R7D0, Q50L43, Q5R5N9, Q5RBE8, Q5RCY5, Q68DD2

Diamond homologs: C8YR32, D3ZKX9, D3ZQF9, F1LQ70, O15296, O16025, O22507, O22508, O24371, O24379, O35936, O70582, O75342, P08170, P09186, P09439, P09917, P09918, P12527, P12530, P16050, P16469, P18054, P24095, P27479, P27480, P27481, P37831, P38414, P38417, P38418, P39654, P39655, P48999, P51399, P55249, Q02759, Q2KMM4, Q41238, Q43190

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CREBBP	“up-regulates quantity by expression”	ALOX15	“transcriptional regulation”
ALOX15	“up-regulates quantity”	15(S)-HETE	“chemical modification”
EP300	“up-regulates quantity by expression”	ALOX15	“transcriptional regulation”
CBP/p300	“up-regulates quantity by expression”	ALOX15	“transcriptional regulation”
STAT6	up-regulates	ALOX15

Disease & clinical

Clinical variants and AI predictions

ClinVar

129 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	102
Likely benign	11
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3391934	GRCh37/hg19 17p13.2(chr17:4354194-5387525)x1	Pathogenic
146235	GRCh38/hg38 17p13.2(chr17:4044302-5943772)x1	Likely pathogenic

SpliceAI

2424 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4631775:GCCAC:G	acceptor_gain	1.0000
17:4631776:CCAC:C	acceptor_gain	1.0000
17:4631776:CCACC:C	acceptor_gain	1.0000
17:4631777:CAC:C	acceptor_gain	1.0000
17:4631777:CACC:C	acceptor_gain	1.0000
17:4631778:AC:A	acceptor_gain	1.0000
17:4631779:CC:C	acceptor_gain	1.0000
17:4631779:CCTGG:C	acceptor_loss	1.0000
17:4631780:C:CC	acceptor_gain	1.0000
17:4631780:CTGGG:C	acceptor_loss	1.0000
17:4631781:T:C	acceptor_loss	1.0000
17:4631859:T:TA	donor_gain	1.0000
17:4631864:AGGGC:A	donor_gain	1.0000
17:4631881:G:C	donor_gain	1.0000
17:4631883:TCTCA:T	donor_loss	1.0000
17:4631884:CTCA:C	donor_loss	1.0000
17:4631885:TCA:T	donor_loss	1.0000
17:4631886:CA:C	donor_loss	1.0000
17:4631887:A:AC	donor_gain	1.0000
17:4631888:C:CC	donor_gain	1.0000
17:4631888:C:CT	donor_loss	1.0000
17:4632052:TCCAG:T	acceptor_gain	1.0000
17:4632053:CCAG:C	acceptor_gain	1.0000
17:4632053:CCAGC:C	acceptor_gain	1.0000
17:4632054:CAG:C	acceptor_gain	1.0000
17:4632054:CAGC:C	acceptor_gain	1.0000
17:4632055:AG:A	acceptor_gain	1.0000
17:4632057:C:CC	acceptor_gain	1.0000
17:4632057:CTAAG:C	acceptor_loss	1.0000
17:4632058:T:C	acceptor_loss	1.0000

AlphaMissense

4294 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4631942:C:G	A586P	0.985
17:4632041:A:G	W553R	0.984
17:4632041:A:T	W553R	0.984
17:4635888:T:A	K344N	0.981
17:4635888:T:G	K344N	0.981
17:4633307:G:C	S419R	0.979
17:4633307:G:T	S419R	0.979
17:4633309:T:G	S419R	0.979
17:4631612:A:C	S659R	0.978
17:4631612:A:T	S659R	0.978
17:4631614:T:G	S659R	0.978
17:4638360:A:G	W222R	0.978
17:4638360:A:T	W222R	0.978
17:4631956:G:T	P581H	0.971
17:4632909:A:G	W498R	0.971
17:4632909:A:T	W498R	0.971
17:4639541:A:G	W76R	0.970
17:4639541:A:T	W76R	0.970
17:4635889:T:A	K344I	0.969
17:4635884:A:G	W346R	0.967
17:4635884:A:T	W346R	0.967
17:4635814:T:A	E369V	0.966
17:4635873:G:C	S349R	0.966
17:4635873:G:T	S349R	0.966
17:4635875:T:G	S349R	0.966
17:4632277:A:C	F515L	0.964
17:4632277:A:T	F515L	0.964
17:4632279:A:G	F515L	0.964
17:4638969:C:A	W141C	0.964
17:4638969:C:G	W141C	0.964

dbSNP variants (sampled 300 via entrez): RS1000103161 (17:4642575 T>A,C), RS1000597015 (17:4636870 A>G), RS1000803437 (17:4632705 C>T), RS1001029871 (17:4638256 G>A,T), RS1002308737 (17:4641618 C>T), RS1002442679 (17:4641437 G>A,C,T), RS1002996068 (17:4638995 A>G), RS1003329906 (17:4640419 C>G), RS1003424840 (17:4639688 C>T), RS1003648947 (17:4634157 G>A), RS1004094127 (17:4637000 G>A,T), RS1004181025 (17:4635197 T>G), RS1005056285 (17:4631159 G>A), RS1005188372 (17:4642883 G>A), RS1005433143 (17:4631491 G>A,C)

Disease associations

OMIM: gene MIM:152392 | disease phenotypes: MIM:208550

GenCC curated gene-disease

Disease	Classification	Inheritance
pregnancy loss, recurrent, susceptibility	Limited	Autosomal recessive

Mondo (2): asthma, nasal polyps, and aspirin intolerance (MONDO:0008834), pregnancy loss, recurrent, susceptibility (MONDO:0000144)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST003141_4	Proteinuria and chronic kidney disease	3.000000e-06
GCST004600_139	Eosinophil percentage of white cells	6.000000e-40
GCST004606_25	Eosinophil count	2.000000e-42
GCST004606_26	Eosinophil count	2.000000e-10
GCST004617_118	Eosinophil percentage of granulocytes	3.000000e-36
GCST004623_82	Neutrophil percentage of granulocytes	3.000000e-32
GCST004624_7	Sum eosinophil basophil counts	2.000000e-39
GCST004624_8	Sum eosinophil basophil counts	4.000000e-09
GCST005038_95	Allergic disease (asthma, hay fever or eczema)	2.000000e-09
GCST007443_1	Nasal polyps	8.000000e-27
GCST007444_3	Chronic rhinosinusitis	1.000000e-08
GCST009719_3	Allergic rhinitis	2.000000e-09
GCST90002381_105	Eosinophil count	2.000000e-39
GCST90002381_106	Eosinophil count	2.000000e-117
GCST90002381_107	Eosinophil count	3.000000e-20
GCST90002381_108	Eosinophil count	1.000000e-12
GCST90002382_407	Eosinophil percentage of white cells	1.000000e-15
GCST90002382_408	Eosinophil percentage of white cells	4.000000e-09
GCST90002382_409	Eosinophil percentage of white cells	2.000000e-117
GCST90002382_410	Eosinophil percentage of white cells	2.000000e-21

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2903 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

174 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 660,831 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1018	DIENESTROL	4	5,607
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1046	AMINOCAPROIC ACID	4	95,343
CHEMBL1103	FURAZOLIDONE	4	14,492
CHEMBL110458	MIGALASTAT	4	430
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,574
CHEMBL11359	CISPLATIN	4
CHEMBL1168	RAMIPRIL	4	46,990
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1200467	HYDROXYZINE PAMOATE	4	7,357
CHEMBL1200468	MALATHION	4	36,800
CHEMBL1200471	PYRITHIONE ZINC	4	24,834
CHEMBL1200522	AVOBENZONE	4	34,067
CHEMBL1200596	CHLOROXINE	4	1,792
CHEMBL1200612	DIBUCAINE HYDROCHLORIDE	4	7,397
CHEMBL1200618	FEXOFENADINE HYDROCHLORIDE	4	6,286
CHEMBL1200787	PHENOXYBENZAMINE HYDROCHLORIDE	4	2,483
CHEMBL1200796	CYCLOPHOSPHAMIDE	4
CHEMBL1200970	ETHOPROPAZINE HYDROCHLORIDE	4
CHEMBL1201022	PHENAZOPYRIDINE HYDROCHLORIDE	4
CHEMBL1201154	PROCHLORPERAZINE EDISYLATE	4
CHEMBL1201236	CARBIDOPA ANHYDROUS	4
CHEMBL1205	NELFINAVIR MESYLATE	4
CHEMBL1206	ETHOPROPAZINE	4
CHEMBL12856	INAMRINONE	4
CHEMBL1321	PROCARBAZINE	4
CHEMBL1334033	PERHEXILINE MALEATE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3892408	ALOX15		0.00	0
rs2619112	ALOX15		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lipoxygenases

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
compound 34 [PMID: 20866075]	Inhibition	8.0	pKi
ML351	Inhibition	6.7	pIC50
PD-146176	Inhibition	6.7	pKi
vatiquinone	Inhibition	6.23	pIC50
PKUMDL_MH_1001	Positive	5.41	pKd

Binding affinities (BindingDB)

22 measured of 60 human assays (61 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-naphthalen-1-yl-5-(propylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	100 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-(ethylamino)-2-naphthalen-1-yl-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	120 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-(butylamino)-2-naphthalen-1-yl-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	120 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-(methylamino)-2-naphthalen-1-yl-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	200 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-naphthalen-1-yl-5-(pentylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	300 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-(2,3-dichlorophenyl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	460 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-(methylamino)-2-naphthalen-1-yl-4,5-dihydro-1,3-thiazole-4-carbonitrile	IC50	550 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-isoquinolin-6-yl-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	730 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
CHEMBL5575619	IC50	740 nM
2-(3,4-dichlorophenyl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	810 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-amino-2-[2-[4-[2-(6,6-dimethyl-2-bicyclo[3.1.1]heptanyl)ethoxy]phenyl]ethyl]propane-1,3-diol	EC50	1240 nM	US-9181182: S1P receptors modulators
2-naphthalen-1-yl-5-(prop-2-enylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	3000 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-(methylamino)-2-quinolin-5-yl-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	3600 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-(1H-indol-3-yl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	3900 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
N-methyl-5-naphthalen-1-yl-2,3-dihydro-1,3,4-oxadiazol-2-amine	IC50	5400 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-(3-chlorophenyl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	6300 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-(1,3-benzodioxol-5-yl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	7600 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
N-(4-cyano-2-naphthalen-1-yl-4,5-dihydro-1,3-oxazol-5-yl)acetamide	IC50	10000 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-(4-fluorophenyl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	15000 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-(methylamino)-2-(2-phenylphenyl)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	23000 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
2-(4-chlorophenyl)-5-(methylamino)-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	25000 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase
5-amino-2-naphthalen-1-yl-4,5-dihydro-1,3-oxazole-4-carbonitrile	IC50	25000 nM	US-10287279: Inhibitors of human 12/15-lipoxygenase

ChEMBL bioactivities

2257 potent at pChembl≥5 of 5926 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL3604156
9.00	Ki	1	nM	CHEMBL3622746
9.00	Potency	1	nM	CHEMBL1515352
8.70	IC50	2	nM	CHEMBL3604185
8.49	Potency	3.2	nM	8-AZAGUANINE
8.47	IC50	3.4	nM	CHEMBL3781002
8.40	IC50	4	nM	CHEMBL3604184
8.30	Potency	5	nM	AMINOCAPROIC ACID
8.30	Potency	5	nM	CHEMBL1406016
8.22	IC50	6	nM	CHEMBL3633564
8.20	Potency	6.3	nM	CHEMBL1419647
8.20	Potency	6.3	nM	CHEMBL1368961
8.20	Potency	6.3	nM	CHEMBL1565492
8.20	Potency	6.3	nM	CHEMBL1466511
8.20	Potency	6.3	nM	CHEMBL1302560
8.20	Potency	6.3	nM	CHEMBL2062275
8.20	Potency	6.3	nM	CHEMBL1303685
8.20	Potency	6.3	nM	CHEMBL1524581
8.20	Potency	6.3	nM	CHEMBL1463242
8.20	Potency	6.3	nM	CHEMBL3194428
8.20	Potency	6.3	nM	CHEMBL1311629
8.20	Potency	6.3	nM	CHEMBL1331287
8.20	Potency	6.3	nM	CHEMBL1509915
8.20	Potency	6.3	nM	CHEMBL1790030
8.10	Potency	7.9	nM	CHEMBL1404006
8.10	Potency	7.9	nM	CHEMBL1377260
8.10	Potency	7.9	nM	CHEMBL1592468
8.10	Potency	7.9	nM	CHEMBL1378090
8.10	Potency	7.9	nM	CHEMBL1309430
8.10	Potency	7.9	nM	ACETAMIDE
8.10	Potency	7.9	nM	CHEMBL1548983
8.00	IC50	10	nM	CHEMBL3604156
8.00	Ki	10	nM	CHEMBL1271117
8.00	Potency	10	nM	DISOPIRAMIDE
8.00	Potency	10	nM	CHEMBL1387552
8.00	Potency	10	nM	CHEMBL1303091
8.00	Potency	10	nM	CHEMBL1344239
8.00	Potency	10	nM	CHEMBL1389294
8.00	Potency	10	nM	CHEMBL1586577
8.00	Potency	10	nM	CHEMBL1503644
8.00	Potency	10	nM	CHEMBL1407493
7.92	IC50	12	nM	CHEMBL4301351
7.90	Potency	12.6	nM	CHEMBL1368759
7.90	Potency	12.6	nM	CHEMBL1438937
7.90	Potency	12.6	nM	MERCURIC CHLORIDE
7.90	Potency	12.6	nM	CHEMBL1526784
7.90	Potency	12.6	nM	CHEMBL1583856
7.90	Potency	12.6	nM	CHEMBL1571970
7.90	Potency	12.6	nM	PHENYLMERCURIC ACETATE
7.89	IC50	13	nM	CHEMBL3290441

PubChem BioAssay actives

433 with measured affinity, of 1681 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-bromo-5-chloro-N-(2-chloro-4-fluorophenyl)-1H-pyrazole-3-carboxamide	1239664: Inhibition of human 15-LOX-1 expressed in Sf9 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0010	uM
2-[4-[2-[[ethyl-[(3S)-1-[1-(4-fluorophenyl)ethyl]pyrrolidin-3-yl]sulfamoyl]amino]ethyl]-5-thiophen-2-yl-1H-pyrazol-3-yl]pyrazine	1250681: Competitive inhibition of human 15-LOX1 using linoleic acid as substrate after 10 mins by Lineweaver-Burk plot analysis	ki	0.0010	uM
6-chloro-2-(4,5-dichloro-1H-pyrazol-3-yl)-1,3-benzoxazole	1239664: Inhibition of human 15-LOX-1 expressed in Sf9 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0020	uM
3-(benzylamino)-4-(cyclohexylamino)-N-ethylbenzenesulfonamide	2106964: Inhibition of 15-LOX (unknown origin)	ic50	0.0034	uM
6-chloro-2-(5-chloro-1H-pyrazol-3-yl)-1,3-benzoxazole	1239664: Inhibition of human 15-LOX-1 expressed in Sf9 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0040	uM
ethyl 3-(benzylamino)-4-(cyclohexylamino)benzoate	2106964: Inhibition of 15-LOX (unknown origin)	ic50	0.0060	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-fluorobenzoate	1250681: Competitive inhibition of human 15-LOX1 using linoleic acid as substrate after 10 mins by Lineweaver-Burk plot analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-methoxybenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-bromobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3,4,5-trichlorothiophene-2-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 1-benzothiophene-3-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3-chlorothiophene-2-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl thiophene-3-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3,4-difluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 2,4-difluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 2-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-(trifluoromethylsulfanyl)benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-(difluoromethoxy)benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-(trifluoromethoxy)benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-(trifluoromethyl)benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl cyclopentanecarboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 1-benzothiophene-2-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[[5-(3-fluorophenyl)-1,3,4-oxadiazol-2-yl]sulfanyl]but-2-ynyl 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]sulfanyl]but-2-ynyl 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]sulfanyl]but-2-ynyl 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-chlorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 2-fluoropyridine-3-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
4-[(5-naphthalen-2-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0100	uM
3-(benzylamino)-4-(cyclohexylamino)-N-(2-piperazin-1-ylethyl)benzenesulfonamide	2106964: Inhibition of 15-LOX (unknown origin)	ic50	0.0120	uM
4-[(E)-2-[3-[(E)-2-[4-hydroxy-3-methoxy-5-(3-methylbut-2-enyl)phenyl]ethenyl]-1H-pyrazol-5-yl]ethenyl]-2-methoxy-6-(3-methylbut-2-enyl)phenol	1155604: Inhibition of 15-LO-mediated 15-HETE formation in LPS-stimulated human monocytes preincubated for 15 mins before arachidonic acid substrate addition measured after 30 mins by UPLC-MS/MS analysis	ic50	0.0130	uM
6-chloro-2-(1H-pyrazol-5-yl)-1,3-benzoxazole	1239666: Inhibition of 15-LOX-1 in human L1236 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0130	uM
4,5-dichloro-N-(2-chloro-4-fluorophenyl)-1H-pyrazole-3-carboxamide	1239666: Inhibition of 15-LOX-1 in human L1236 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0140	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 1-benzofuran-2-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0150	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-(dimethylamino)benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0150	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3,4,5-trifluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0160	uM
1-(1,3-benzodioxol-5-ylcarbamothioyl)-N-(2-chloro-4-fluorophenyl)pyrazole-3-carboxamide	1236974: Inhibition of human 15-LOX-1 using arachidonic acid as substrate by cell based assay	ic50	0.0170	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl thiophene-2-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0190	uM
N-[2-[2-(1-benzofuran-2-yl)-1H-indol-3-yl]ethyl]-4-pentylbenzenesulfonamide	1250681: Competitive inhibition of human 15-LOX1 using linoleic acid as substrate after 10 mins by Lineweaver-Burk plot analysis	ki	0.0210	uM
5-chloro-N-(2-chloro-4-fluorophenyl)-1H-pyrazole-3-carboxamide	1239666: Inhibition of 15-LOX-1 in human L1236 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0220	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl naphthalene-2-carboxylate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0220	uM
4-[[5-(1H-indol-2-yl)-1,3,4-oxadiazol-2-yl]sulfanyl]but-2-ynyl 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0230	uM
N-(2-chloro-4-fluorophenyl)-1H-pyrazole-5-carboxamide	1239666: Inhibition of 15-LOX-1 in human L1236 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0240	uM
N-(5-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide	1239664: Inhibition of human 15-LOX-1 expressed in Sf9 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0260	uM
4-[(5-phenyl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0260	uM
[(E)-4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-enyl] 4-fluorobenzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0260	uM
N-(2-chloro-4-fluorophenyl)-5-iodo-1H-pyrazole-3-carboxamide	1239666: Inhibition of 15-LOX-1 in human L1236 cells assessed as reduction in conversion of arachidonic acid to 15-HETE pre-incubated 5 min before arachidonic acid substrate addition by HPLC-UV spectroscopy	ic50	0.0270	uM
4-[(5-naphthalen-1-yl-1,3,4-oxadiazol-2-yl)sulfanyl]but-2-ynyl 3-(trifluoromethyl)benzoate	527531: Inhibition of human N-terminal His6-tagged reticulocyte 15-lipoxygenase-1 after 15 mins by UV-vis spectrophotometer analysis	ki	0.0270	uM
ethyl 6-chloro-3-[(3S)-3,7-dimethyloctanoyl]-1H-indole-2-carboxylate	1250681: Competitive inhibition of human 15-LOX1 using linoleic acid as substrate after 10 mins by Lineweaver-Burk plot analysis	ki	0.0300	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
caffeic acid	decreases reaction, increases activity, decreases activity, decreases chemical synthesis, increases abundance	3
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	decreases reaction, increases activity, increases expression, increases chemical synthesis	3
Arachidonic Acid	affects metabolic processing, increases metabolic processing, affects cotreatment, increases activity, increases expression	3
13-hydroxy-9,11-octadecadienoic acid	decreases activity, decreases chemical synthesis, increases abundance, increases chemical synthesis, increases expression	2
sulindac sulfone	decreases reaction, increases phosphorylation, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Sulindac	increases chemical synthesis, increases activity, increases expression	2
Valproic Acid	increases methylation, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
honokiol	decreases expression, increases reaction, increases expression, increases abundance	1
baicalein	decreases activity	1
bisphenol A	affects cotreatment, increases methylation, affects methylation	1
esculetin	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	affects expression	1
perfluorooctanoic acid	decreases expression	1
sulindac sulfide	increases expression	1
15-hydroxy-5,8,11,13-eicosatetraenoic acid	increases abundance	1
adolapin	decreases activity	1
EPTC	affects response to substance	1
8-((4-chlorophenyl)thio)cyclic-3’,5’-GMP	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
8-(4-chlorophenylthio)guanosine 3’,5’-cyclic monophosphorothioate	decreases reaction, increases phosphorylation	1
3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole	increases expression	1
(5-fluoro-2-methyl-1-(4-pyridyl)methylene-3-(N-benzyl)-indene)-acetamide hydrochloride	increases expression	1
hydroxyoctadecadienoic acid	increases abundance, increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects binding, decreases activity	1

ChEMBL screening assays

242 unique, capped per target: 236 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032552	Binding	Inhibition of 15-lipoxygenase	Enzyme inhibitors: new and known polybrominated phenols and diphenyl ethers from four Indo-Pacific Dysidea sponges. — J Nat Prod
CHEMBL1613802	Functional	PUBCHEM_BIOASSAY: Cuvette-Based Assay fo Inhibitors of 15-hLO-1 (15-human lipoxygenase 1): Series 1 - Round 1. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2169, AID887]	PubChem BioAssay data set
CHEMBL4351296	ADMET	Inhibition of 15-lipoxygenase (unknown origin)	Novel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7ZQ	HAP1 ALOX15 (-) 1	Cancer cell line	Male
CVCL_C7ZR	HAP1 ALOX15 (-) 2	Cancer cell line	Male
CVCL_C7ZS	HAP1 ALOX15 (-) 3	Cancer cell line	Male
CVCL_DX23	HAP1 ALOX12 (-) ALOX15 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01681615	Not specified	UNKNOWN	Challenge Test for Acetylsalicylic Acid Hypersensitivity
NCT02064738	Not specified	COMPLETED	High Omega-3/Low Omega-6 Treatment Diet for Aspirin-exacerbated Respiratory Disease (AERD)