ALOX5

Summary

ALOX5 (arachidonate 5-lipoxygenase, HGNC:435) is a protein-coding gene on chromosome 10q11.21, encoding Polyunsaturated fatty acid 5-lipoxygenase (P09917). Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent m….

This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 240 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 124 total — 1 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:435
Approved symbol	ALOX5
Name	arachidonate 5-lipoxygenase
Location	10q11.21
Locus type	gene with protein product
Status	Approved
Aliases	5-LOX
Ensembl gene	ENSG00000012779
Ensembl biotype	protein_coding
OMIM	152390
Entrez	240

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000374391, ENST00000475300, ENST00000481117, ENST00000483623, ENST00000493336, ENST00000498461, ENST00000542434, ENST00000851642, ENST00000851643, ENST00000851644, ENST00000851645, ENST00000851646, ENST00000851647, ENST00000851648, ENST00000961187, ENST00000961188, ENST00000961189, ENST00000961190, ENST00000961191, ENST00000961192

RefSeq mRNA: 5 — MANE Select: NM_000698 NM_000698, NM_001256153, NM_001256154, NM_001320861, NM_001320862

CCDS: CCDS58078, CCDS7212

Canonical transcript exons

ENST00000374391 — 14 exons

Exon	Start	End
ENSE00001728506	45374216	45374429
ENSE00002435024	45428618	45428764
ENSE00002464130	45395855	45395936
ENSE00002467770	45382483	45382681
ENSE00002474736	45441344	45441430
ENSE00002477722	45445508	45446117
ENSE00002497216	45424041	45424147
ENSE00002498943	45412191	45412313
ENSE00002515467	45444116	45444286
ENSE00002523256	45443416	45443537
ENSE00002525684	45443038	45443216
ENSE00003499219	45440430	45440633
ENSE00003651293	45424960	45425132
ENSE00003676213	45443728	45443828

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.18.

FANTOM5 (CAGE): breadth broad, TPM avg 18.6342 / max 1306.3834, expressed in 665 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104785	13.1808	575
104784	3.4110	423
104786	1.9488	293
104787	0.0936	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.18	gold quality
granulocyte	CL:0000094	98.88	gold quality
right lung	UBERON:0002167	98.71	gold quality
monocyte	CL:0000576	98.61	gold quality
spleen	UBERON:0002106	98.58	gold quality
leukocyte	CL:0000738	98.52	gold quality
upper lobe of left lung	UBERON:0008952	98.05	gold quality
vermiform appendix	UBERON:0001154	97.38	gold quality
bone marrow	UBERON:0002371	96.93	gold quality
gall bladder	UBERON:0002110	95.50	gold quality
bone marrow cell	CL:0002092	95.49	gold quality
lymph node	UBERON:0000029	94.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.99	gold quality
lung	UBERON:0002048	92.80	gold quality
small intestine	UBERON:0002108	92.55	gold quality
left uterine tube	UBERON:0001303	92.34	gold quality
cerebellum	UBERON:0002037	91.72	gold quality
cerebellar hemisphere	UBERON:0002245	91.72	gold quality
cerebellar cortex	UBERON:0002129	91.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.67	gold quality
body of pancreas	UBERON:0001150	91.33	gold quality
right coronary artery	UBERON:0001625	91.23	gold quality
urinary bladder	UBERON:0001255	90.81	gold quality
minor salivary gland	UBERON:0001830	90.69	gold quality
mucosa of stomach	UBERON:0001199	90.65	gold quality
saliva-secreting gland	UBERON:0001044	89.90	gold quality
omental fat pad	UBERON:0010414	89.51	gold quality
adipose tissue	UBERON:0001013	88.99	gold quality
right adrenal gland cortex	UBERON:0035827	88.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.84	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	522.50
E-HCAD-6	yes	177.98
E-MTAB-6678	yes	40.11
E-ANND-3	yes	17.44
E-CURD-122	yes	12.75
E-CURD-112	yes	11.86
E-MTAB-8498	yes	10.12
E-MTAB-8410	yes	8.99
E-MTAB-5061	yes	4.51
E-MTAB-9801	yes	4.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, HDAC2, HDAC3, IRF6, MBD1, MBD2, MECP2, MYB, NFKB1, NFKB, RARA, RELA, RORA, SP1, SP3, TP53, VDR, ZNF263

miRNA regulators (miRDB)

20 targeting ALOX5, 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-3646	100.00	73.56	5283
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-1225-5P	96.76	66.85	417
HSA-MIR-4529-3P	96.40	66.46	582
HSA-MIR-5002-3P	95.75	67.04	542

Literature-anchored findings (GeneRIF, showing 40)

• molecular basis of the specific subcellular localization of the C2-like domain (PMID:11796736)
• promotion of phosphorylation at Ser-271 by MAPK-activated protein kinase 2 and arachidonic acid (PMID:11844797)
• Theoretical model of the tertiary structure of the 5-lipoxygenase catalytic domain, using the resolved structure of rabbit 15-lipoxygenase as a template. (PMID:12111389)
• Data show that the previously identified bipartite-motif region within 5-lipoxygenase is not a functional import sequence, whereas the newly identified basic region constitutes a true nuclear import sequence. (PMID:12140292)
• marked expression of 5-LOX in human pancreatic cancer tissues (PMID:12163367)
• there is no evidence of increased expression of 5-LO mRNA in either quiescent or active stages of inflammatory bowel disease (PMID:12234060)
• results demonstrating mechanisms for activation of 5-LO differ considerably between cell types (PMID:12525578)
• LOX5 and FLAP pathway in monocytes and microglia yields products toxic toward neurons (neuroblastoma cell line) (PMID:12629151)
• examines the binding of calcium to this enzyme (REVIEW) (PMID:12664574)
• CON6 mouse point mutations (I645V and V646I) as well as the double mutant (I645V+V646I) introduced by site-directed mutagenesis into human 5-LO exhibited reduced catalytic activities but retained their positional specificity & substrate affinity. (PMID:12730086)
• LTC4 production by eosinophils in asthmatic subjects with alternative forms of ALOX-5 core promoter (PMID:12751728)
• upregulated in colon cancer; affecting cell survival (PMID:12751768)
• upregulation in glioblastoma multiforme (PMID:12751769)
• Data show that inhibition of arachidonate 5-lipoxygenase induces rapid activation of c-Jun N-terminal kinase (JNK) in human prostate cancer cells which is prevented by the 5-lipoxygenase metabolite, 5(S)-HETE. (PMID:12859962)
• 5-lipoxygenase can be activated by calcium and low levels of hydroperoxides (PMID:12893830)
• human breast tumours aberrantly express significantly higher levels of 5-lipoxygenase; levels of 5-lipoxygenases were also particularly high in tumours from patients who died of breast cancer. (PMID:12907138)
• Lipoxygenase is induced in bladder cancer. Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. (PMID:14532840)
• possible involvement of 5-lipoxygenase (ALOX5) gene polymorphism in ASA-intolerant asthma (AIA) in a Korean population (PMID:14749922)
• increased expressions of 5-LOX and 12-LOX were detected in testicular cancer tissues (PMID:14767568)
• Up-regulation of 5-Lipoxygenase is associated with prostate cancer (PMID:15010818)
• determination of binding sites for calcium and magnesium (PMID:15219851)
• PKA phosphorylates 5-LO on Ser-523, which inhibits the catalytic activity of 5-LO and reduces cellular LT generation (PMID:15280375)
• Expression of 5-lipoxygenase mRNA was observed in muscle tissues from patients with idiopathic inflammatory myopathies suggesting a role in pathogenesis of this disease. (PMID:15301234)
• polymorphisms in arachidonate 5-lipoxygenase is associated with colon cancer risk (PMID:15308583)
• Data show that 5-lipoxygenase activity increases during senescence-like growth arrest via a p53/p21-dependent pathway in both human and mouse embryo fibroblasts. (PMID:15616590)
• Increased 5-lipoxygenase expression is associated with esophageal cancer (PMID:15661803)
• Mutagenesis of 5LO C-terminal mutants showed that hidrogen bonds are required for a stabilizing C-terminal loop. (PMID:15848143)
• In the absence of Ca2+ (chelated using EDTA), OAG strongly and concentration-dependently stimulated 5-LO enzyme from polymorphonuclear leukocytes (PMID:15923196)
• The expression of 5-LO is elevated in symptomatic compared with asymptomatic plaques and is associated with acute ischemic syndromes (PMID:15933245)
• results suggest that splitting of BL41-E95-A cells induces de novo synthesis of a protein involved in the activation of casp-6 and casp-8, which cleaves 5-LO. (PMID:16135563)
• Nuclear export of 5-LO depends on the stress-induced activation of the p38 MAPK pathway. (PMID:16165096)
• Arachidonic acid regulates the translocation of 5-LO in human neutophild unraveling a novel mechanism of the cAMP-mediated inhibition of leukotriene biosynthesis (PMID:16275640)
• the polymorphism of ALOX5 at positions of -1708 G > A showed significant difference in genotype frequency between aspirin-intolerant urticaria and aspirin-intolerant asthma (PMID:16361798)
• mizolastine down-regulated 5-LOX mRNA expression and inhibited 5-LOX translocation from nucleus to cytoplasm in fibroblasts (PMID:16402861)
• the GC-rich part of the 5-lipoxygenase gene promoter, including a novel Sp1 site, appear important for basal (rather than upregulated) transcription of 5-lipoxygenase gene in monocytic cells (PMID:16413224)
• a critical regulatory role of arachidonate reacylation that limits leukotriene biosynthesis in concert with 5-lipoxygenase and cytosolic phospholipase A(2)alpha activation (PMID:16495221)
• Administration of omega-3 reduced significantly ALOX5 activity, with no effect on ALOX5 protein expression. (PMID:16531984)
• The binding between human 5-lipoxygenase with its inhibitors can be investigated by SPR technology and molecular docking simulation. (PMID:16672272)
• 5-lipoxygenase and leukotriene A4 hydrolase expression in atherosclerotic lesions correlates with symptoms of plaque instability (PMID:16698924)
• The stratified squamous epithelial cells from inflamed or hyperplastic tissues of palatine and pharyngeal tonsils (nasopharyngeal-associated lymphoid tissue) express 5-lipoxygenase protein. (PMID:16733792)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	alox5b.1	ENSDARG00000043085
danio_rerio	alox5b.2	ENSDARG00000043089
danio_rerio	alox5a	ENSDARG00000057273
danio_rerio	alox5b.3	ENSDARG00000069966
mus_musculus	Alox5	ENSMUSG00000025701
rattus_norvegicus	Alox5	ENSRNOG00000012972

Paralogs (5): ALOX12 (ENSG00000108839), ALOX15 (ENSG00000161905), ALOXE3 (ENSG00000179148), ALOX12B (ENSG00000179477), ALOX15B (ENSG00000179593)

Protein

Protein identifiers

Polyunsaturated fatty acid 5-lipoxygenase — P09917 (reviewed: P09917)

Alternative names: Arachidonate 5-lipoxygenase

All UniProt accessions (1): P09917

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation. Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene. Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses. Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers. In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes. Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40. May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK. Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells.

Subunit / interactions. Homodimer. Interacts with ALOX5AP and LTC4S. Interacts with COTL1, the interaction is required for stability and efficient catalytic activity. Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS). Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1.

Subcellular location. Cytoplasm. Nucleus matrix. Nucleus membrane. Perinuclear region. Cytosol. Nucleus envelope. Nucleus intermembrane space.

Post-translational modifications. Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-524 by PKA has an inhibitory effect. Phosphorylation on Ser-272 prevents export from the nucleus. Phosphorylation at Ser-524 is stimulated by 8-bromo-3’,5’-cyclic AMP or prostaglandin E2.

Activity regulation. Undergoes a sequential loss of the oxygenase and pseudoperoxidase activities which is dependent on the structural characteristics of the substrate for the reaction, on oxygen concentration and on exposure to phospholipids and calcium. 15-HETE and other 15-mono-hydroxyeicosanoids exhibit the highest inhibitory potencies in their capability of suppressing 5-lipoxygenation of arachidonic acid, whereas the other HETEs, (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5,15-diHETE) as well as octadecanoids, are modest or poor inhibitors. The formation of (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate is strongly stimulated by either hydroperoxypolyenoic fatty acids or arachidonic acid. Arachidonate 5-lipoxygenase and leukotriene A4 synthase activities are allosterically increased by ATP.

Cofactor. Binds 1 Fe cation per subunit.

Pathway. Lipid metabolism; leukotriene A4 biosynthesis.

Similarity. Belongs to the lipoxygenase family.

Isoforms (5)

UniProt ID	Names	Canonical?
P09917-1	1	yes
P09917-2	2, Delta-13
P09917-3	3, delta-p10
P09917-4	4, delta-10-13
P09917-5	5, alpha-10

RefSeq proteins (5): NP_000689, NP_001243082, NP_001243083, NP_001307790, NP_001307791 (=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 1.13.11.34 — arachidonate 5-lipoxygenase (BRENDA: 14 organisms, 69 substrates, 724 inhibitors, 35 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ARACHIDONIC ACID	0.012–0.182	10
ARACHIDONATE	0.0033–0.06	8
LINOLEIC ACID	0.004–0.2	3
(5S,6E,8Z,11Z,14Z)-5-HYDROPEROXYICOSA-6,8,11,14-	0.014–0.019	2
5,8,11,14,17-EICOSAPENTAENOIC ACID	0.013–0.024	2
7,7-D2-ARACHIDONATE	0.0093–0.0114	2
1-LINOLEOYL LYSOPHOSPHATIDIC ACID	0.002	1
1-LINOLEOYL LYSOPHOSPHATIDYLCHOLINE	0.003	1
5,8,11-EICOSATRIENOIC ACID	0.032	1
8,11,14-EICOSATRIENOIC ACID	0.09	1
BISHOMO-GAMMA-LINOLENIC ACID	0.05	1

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 = (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (RHEA:17485)
• (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = leukotriene A4 + H2O (RHEA:17961)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = leukotriene A4 + H2O (RHEA:32307)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate (RHEA:38675)
• (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O (RHEA:39107)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate (RHEA:41332)
• (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate (RHEA:48624)
• 18-HEPE + O2 = (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate (RHEA:48860)
• (18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate (RHEA:50204)
• (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O (RHEA:50268)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate (RHEA:50840)

UniProt features (115 total): helix 36, mutagenesis site 22, strand 21, binding site 13, sequence variant 7, turn 5, splice variant 5, domain 2, modified residue 2, chain 1, site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7TTK	X-RAY DIFFRACTION	1.98
3V98	X-RAY DIFFRACTION	2.07
7TTJ	X-RAY DIFFRACTION	2.1
3V99	X-RAY DIFFRACTION	2.25
3O8Y	X-RAY DIFFRACTION	2.39
7TTL	X-RAY DIFFRACTION	2.43
6N2W	X-RAY DIFFRACTION	2.71
3V92	X-RAY DIFFRACTION	2.74
6NCF	X-RAY DIFFRACTION	2.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09917-F1	97.24	0.96

Functional residue map

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

Catalytic / active sites (1): 103 (essential for stabilizing binding to cotl1)

Ligand- & substrate-binding residues (13): 80; 368; 373; 551; 555; 674; 17; 18; 19; 44; 45; 47 …

Post-translational modifications (2): 272, 524

Mutagenesis-validated functional residues (22):

Position	Phenotype
14	impairs interaction with dicer1; when associated with a-76 and a-103.
76	impairs interaction with dicer1; when associated with a-14 and a-103.
103	abolishes binding to cotl1. impairs interaction with dicer; when associated with a-14 and a-76.
272	loss of phosphorylation site. permits export from the nucleus.
359	no loss of activity.
360	loss of (5s)-lipoxygenase activity; when associated with i-425 and m-426. loss of (5s)-lipoxygenase activity; when assoc
363	still some substantial activity.
368	no activity.
373	no activity.
377	no activity.
391	no activity.
391	still some substantial activity.
400	no activity.
400	still some substantial activity.
425	loss of (5s)-lipoxygenase activity; when associated with w-360 and m-426. loss of (5s)-lipoxygenase activity; when assoc
426	loss of (5s)-lipoxygenase activity; when associated with w-360 and i-425. loss of (5s)-lipoxygenase activity; when assoc
433	almost no loss of activity.
524	prevents phosphorylation by pka.
551	no activity.
604	loss of (5s)-lipoxygenase activity. loss of (5s)-lipoxygenase activity; when associated with w-360; i-425 and m-426. exh
664	does not affect arachidonate 5-lipoxygenase activity. does not oxygenate arachidonate typical 15-lipoxygenase substrates
664	enhances affinity for arachidonic acid. impairs arachidonate 5-lipoxygenase activity. induces arachidonate 15-lipoxygena

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-2142688	Synthesis of 5-eicosatetraenoic acids
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142700	Biosynthesis of Lipoxins (LX)
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-9012546	Interleukin-18 signaling
R-HSA-9018676	Biosynthesis of D-series resolvins
R-HSA-9018682	Biosynthesis of maresins
R-HSA-9018896	Biosynthesis of E-series 18(S)-resolvins
R-HSA-9020265	Biosynthesis of aspirin-triggered D-series resolvins
R-HSA-9023661	Biosynthesis of E-series 18(R)-resolvins
R-HSA-9026286	Biosynthesis of DPAn-3-derived protectins and resolvins
R-HSA-9026290	Biosynthesis of DPAn-3-derived maresins
R-HSA-9026403	Biosynthesis of DPAn-3-derived 13-series resolvins
R-HSA-9027604	Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2142753	Arachidonate metabolism
R-HSA-446652	Interleukin-1 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9018677	Biosynthesis of DHA-derived SPMs
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: 406 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_DENDRITIC_CELL_MIGRATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CELL_CHEMOTAXIS, LU_IL4_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE

GO Biological Process (35): negative regulation of endothelial cell proliferation (GO:0001937), leukocyte chemotaxis involved in inflammatory response (GO:0002232), leukocyte migration involved in inflammatory response (GO:0002523), leukotriene production involved in inflammatory response (GO:0002540), leukotriene metabolic process (GO:0006691), humoral immune response (GO:0006959), negative regulation of angiogenesis (GO:0016525), arachidonate metabolic process (GO:0019369), leukotriene biosynthetic process (GO:0019370), lipoxygenase pathway (GO:0019372), positive regulation of bone mineralization (GO:0030501), lipid oxidation (GO:0034440), dendritic cell migration (GO:0036336), glucose homeostasis (GO:0042593), long-chain fatty acid biosynthetic process (GO:0042759), regulation of fat cell differentiation (GO:0045598), regulation of inflammatory response (GO:0050727), negative regulation of inflammatory response (GO:0050728), regulation of insulin secretion (GO:0050796), negative regulation of vascular wound healing (GO:0061044), negative regulation of wound healing (GO:0061045), regulation of inflammatory response to wounding (GO:0106014), regulation of cytokine production involved in inflammatory response (GO:1900015), regulation of cellular response to oxidative stress (GO:1900407), leukotriene A4 biosynthetic process (GO:1901753), regulation of reactive oxygen species biosynthetic process (GO:1903426), negative regulation of response to endoplasmic reticulum stress (GO:1903573), negative regulation of sprouting angiogenesis (GO:1903671), positive regulation of leukocyte adhesion to arterial endothelial cell (GO:1904999), lipoxin biosynthetic process (GO:2001301), long-chain fatty acid metabolic process (GO:0001676), lipid metabolic process (GO:0006629), icosanoid metabolic process (GO:0006690), response to stress (GO:0006950), inflammatory response (GO:0006954)

GO Molecular Function (11): arachidonate 5-lipoxygenase activity (GO:0004051), arachidonate 12(S)-lipoxygenase activity (GO:0004052), iron ion binding (GO:0005506), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen (GO:0016701), hydrolase activity (GO:0016787), arachidonate 8(S)-lipoxygenase activity (GO:0036403), protein binding (GO:0005515), 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 (14): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nuclear envelope (GO:0005635), nuclear envelope lumen (GO:0005641), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear matrix (GO:0016363), nuclear membrane (GO:0031965), secretory granule lumen (GO:0034774), perinuclear region of cytoplasm (GO:0048471), ficolin-1-rich granule lumen (GO:1904813), nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Biosynthesis of DHA-derived SPMs	3
Biosynthesis of DPAn-3 SPMs	3
Arachidonate metabolism	2
Biosynthesis of specialized proresolving mediators (SPMs)	2
Biosynthesis of EPA-derived SPMs	2
Immune System	2
Signaling by Interleukins	1
Innate Immune System	1
Interleukin-1 family signaling	1
Fatty acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
inflammatory response	4
icosanoid metabolic process	3
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	3
long-chain fatty acid metabolic process	2
catalytic activity	2
oxidoreductase activity	2
nucleus	2
nuclear envelope	2
nuclear lumen	2
cytoplasm	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
leukocyte migration involved in inflammatory response	1
leukocyte chemotaxis	1
leukocyte migration	1
arachidonate metabolite production involved in inflammatory response	1
immune response	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
leukotriene metabolic process	1
icosanoid biosynthetic process	1
fatty acid metabolic process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
lipid modification	1
mononuclear cell migration	1
carbohydrate homeostasis	1
fatty acid biosynthetic process	1
fat cell differentiation	1
regulation of cell differentiation	1
regulation of defense response	1
regulation of response to external stimulus	1
negative regulation of defense response	1

Protein interactions and networks

STRING

2422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALOX5	ALOX5AP	P20292	991
ALOX5	COTL1	Q14019	945
ALOX5	LTA4H	P09960	925
ALOX5	LTC4S	Q16873	812
ALOX5	PLA2G4A	P47712	783
ALOX5	LOX	P28300	776
ALOX5	CYSLTR1	Q9Y271	762
ALOX5	PTGS2	P35354	742
ALOX5	LTB4R	Q15722	720
ALOX5	PTGS1	P23219	693
ALOX5	CYSLTR2	Q9NS75	670
ALOX5	LTB4R2	Q9NPC1	667
ALOX5	PTGES	O14684	666
ALOX5	MMP2	P08253	646
ALOX5	STAT3	P40763	604

IntAct

113 interactions, top by confidence:

A	B	Type	Score
MAD1L1	ALOX5	psi-mi:“MI:0915”(physical association)	0.810
ALOX5	MAD1L1	psi-mi:“MI:0915”(physical association)	0.810
HHIPL2	ALOX5	psi-mi:“MI:0915”(physical association)	0.720
SYCE1	ALOX5	psi-mi:“MI:0915”(physical association)	0.720
ALOX5	HHIPL2	psi-mi:“MI:0915”(physical association)	0.720
ALOX5	SYCE1	psi-mi:“MI:0915”(physical association)	0.720
ALOX5	CEP63	psi-mi:“MI:0915”(physical association)	0.720
COTL1	ALOX5	psi-mi:“MI:0407”(direct interaction)	0.700
ALOX5	COTL1	psi-mi:“MI:0915”(physical association)	0.700
ALOX5	NUTM1	psi-mi:“MI:0915”(physical association)	0.670
ALOX5	CEP63	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (135): ALOX5 (Reconstituted Complex), MEOX1 (Two-hybrid), REL (Two-hybrid), MAD1L1 (Two-hybrid), HHIPL2 (Two-hybrid), CEP63 (Two-hybrid), SYCE1 (Two-hybrid), NUTM1 (Two-hybrid), CEP57L1 (Two-hybrid), ALOX5AP (Co-localization), ALOX5 (Reconstituted Complex), ALOX5 (Affinity Capture-Western), ALOX5 (Reconstituted Complex), CEP57L1 (Two-hybrid), CEP63 (Two-hybrid)

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: A2RSQ0, B8UU59, C8YR32, E7FKV8, G3V7Q0, O08852, O16025, P09917, P12527, P48999, P51399, P98161, Q09624, Q2EG98, Q6IQ26, Q6NXD8, Q6PAL8, Q6ZUT9, Q7TN88, Q7Z442, Q7Z443, Q8IVV2, Q8R526, Q8TDX9, Q9NTG1, Q9Z0T6, D3ZKX9, D3ZQF9, F1LQ70, O15296, O22507, O22508, O24371, O24379, O35936, O70582, O75342, P08170, P09186, P09439

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
ALOX5	up-regulates	“leukotriene A4”	“chemical modification”
MBD2	“down-regulates quantity by repression”	ALOX5	“transcriptional regulation”
MBD1	“down-regulates quantity by repression”	ALOX5	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	ALOX5	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	ALOX5	“transcriptional regulation”
CAMK2A	“up-regulates activity”	ALOX5	phosphorylation
MAPK1	“up-regulates activity”	ALOX5	phosphorylation
MAPK3	“up-regulates activity”	ALOX5	phosphorylation
ERK1/2	“up-regulates activity”	ALOX5	phosphorylation
Gbeta	“up-regulates activity”	ALOX5	phosphorylation
zileuton	“down-regulates activity”	ALOX5	“chemical inhibition”
MAPKAPK2	“up-regulates activity”	ALOX5	phosphorylation
PRKACA	“down-regulates activity”	ALOX5	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	84
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
624469	GRCh37/hg19 10p11.21-q11.22(chr10:37149872-46169876)x3	Likely pathogenic

SpliceAI

2435 predictions. Top by Δscore:

Variant	Effect	Δscore
10:45382479:CCA:C	acceptor_loss	1.0000
10:45382480:CAGGT:C	acceptor_loss	1.0000
10:45382481:A:AG	acceptor_gain	1.0000
10:45382481:AG:A	acceptor_gain	1.0000
10:45382481:AGGT:A	acceptor_gain	1.0000
10:45382481:AGGTG:A	acceptor_gain	1.0000
10:45382482:G:GA	acceptor_gain	1.0000
10:45382482:GG:G	acceptor_gain	1.0000
10:45382482:GGT:G	acceptor_gain	1.0000
10:45382482:GGTG:G	acceptor_gain	1.0000
10:45382482:GGTGG:G	acceptor_gain	1.0000
10:45395853:A:AG	acceptor_gain	1.0000
10:45395854:G:GG	acceptor_gain	1.0000
10:45395854:GCAA:G	acceptor_gain	1.0000
10:45395854:GCAAA:G	acceptor_gain	1.0000
10:45395937:G:GG	donor_gain	1.0000
10:45412184:T:G	acceptor_gain	1.0000
10:45412185:GCTCA:G	acceptor_loss	1.0000
10:45412186:CTCA:C	acceptor_loss	1.0000
10:45412187:TCAG:T	acceptor_loss	1.0000
10:45412188:CA:C	acceptor_loss	1.0000
10:45412190:G:GT	acceptor_loss	1.0000
10:45412312:GC:G	donor_gain	1.0000
10:45412314:G:GG	donor_gain	1.0000
10:45424039:AG:A	acceptor_gain	1.0000
10:45424039:AGGAT:A	acceptor_gain	1.0000
10:45424040:GG:G	acceptor_gain	1.0000
10:45424040:GGATG:G	acceptor_gain	1.0000
10:45424144:TCTGG:T	donor_loss	1.0000
10:45424148:G:GG	donor_gain	1.0000

AlphaMissense

4477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:45382573:T:A	W81R	1.000
10:45382573:T:C	W81R	1.000
10:45412267:T:C	F170L	1.000
10:45412269:T:A	F170L	1.000
10:45412269:T:G	F170L	1.000
10:45424090:T:A	W202R	1.000
10:45424090:T:C	W202R	1.000
10:45440554:T:C	L369P	1.000
10:45440565:C:G	H373D	1.000
10:45440567:T:A	H373Q	1.000
10:45440567:T:G	H373Q	1.000
10:45441382:C:A	N408K	1.000
10:45441382:C:G	N408K	1.000
10:45441392:C:A	R412S	1.000
10:45441393:G:C	R412P	1.000
10:45441402:T:C	L415P	1.000
10:45443819:C:A	N555K	1.000
10:45443819:C:G	N555K	1.000
10:45374296:T:A	V6D	0.999
10:45382639:T:A	W103R	0.999
10:45382639:T:C	W103R	0.999
10:45382641:G:C	W103C	0.999
10:45382641:G:T	W103C	0.999
10:45395900:G:C	R132P	0.999
10:45395921:G:C	R139P	0.999
10:45412192:T:A	W145R	0.999
10:45412192:T:C	W145R	0.999
10:45412250:T:C	L164S	0.999
10:45412268:T:C	F170S	0.999
10:45412268:T:G	F170C	0.999

dbSNP variants (sampled 300 via entrez): RS1000009544 (10:45439395 G>C), RS1000019056 (10:45403506 C>T), RS1000063634 (10:45426506 A>G), RS1000068027 (10:45431835 G>A), RS1000098750 (10:45431633 C>T), RS1000124232 (10:45378575 C>T), RS1000148969 (10:45436169 A>G), RS1000182084 (10:45435738 A>T), RS1000208327 (10:45392999 T>G), RS1000291800 (10:45373416 C>T), RS1000371683 (10:45443928 C>A,T), RS1000412984 (10:45424000 A>G,T), RS1000437952 (10:45401597 A>G), RS1000472971 (10:45442329 C>T), RS1000485130 (10:45388358 G>A)

Disease associations

OMIM: gene MIM:152390 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001426	Non-Mendelian inheritance
HP:0002099	Asthma
HP:0032933	Airway hyperresponsiveness
HP:4000007	Bronchoconstriction

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000585_14	Mean corpuscular volume	3.000000e-11
GCST000587_14	Mean corpuscular hemoglobin	4.000000e-12
GCST002221_67	Cholesterol, total	8.000000e-09
GCST002223_44	HDL cholesterol	2.000000e-10
GCST004232_71	HDL cholesterol levels	7.000000e-09
GCST004235_55	Total cholesterol levels	1.000000e-07
GCST90002387_353	Immature fraction of reticulocytes	6.000000e-11
GCST90002390_486	Mean corpuscular hemoglobin	4.000000e-27
GCST90011898_73	Alanine aminotransferase levels	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004574	total cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111402 (PROTEIN COMPLEX), CHEMBL215 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 886,339 (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
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1200596	CHLOROXINE	4	1,792
CHEMBL294199	CAPSAICIN	4	52,939
CHEMBL443605	HEXYLRESORCINOL	4	10,669
CHEMBL521	IBUPROFEN	4	228,490
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL93	ZILEUTON	4	21,372
CHEMBL140	CURCUMIN	3	93,882
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL165	RESVERATROL	3	60,144
CHEMBL1922660	FIBOFLAPON	3	303
CHEMBL1950045	HYDROXYTYROSOL	3	6,641
CHEMBL50	QUERCETIN	3	74,559
CHEMBL88712	VELIFLAPON	3	637
CHEMBL16596	QUIFLAPON	2	694
CHEMBL13878	TEBUFELONE	2	3,702
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL154139	TAGORIZINE	2	223
CHEMBL162358	TOMELUKAST	2	1,180
CHEMBL2105653	SETILEUTON	2	74
CHEMBL230006	ENOXOLONE	2
CHEMBL253896	XANTHOHUMOL	2
CHEMBL293743	FENLEUTON	2
CHEMBL300982	LICOFELONE	2
CHEMBL304818	DOCEBENONE	2
CHEMBL316040	TEPOXALIN	2
CHEMBL4078588	MK-7622	2
CHEMBL43185	PIPERINE	2
CHEMBL46469	ANTHRALIN	2
CHEMBL57358	ENOFELAST	2

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2115819	Efficacy	3	montelukast	Asthma

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2115819	ALOX5	3	1.75	1	montelukast
rs1051713	ALOX5		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Lipoxygenases

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
CJ13610	Inhibition	7.15	pIC50
2-TEDC	Inhibition	7.05	pIC50
BW B70C	Inhibition	6.7	pIC50
PF-04191834	Inhibition	6.64	pIC50
5-LOX inhibitor 2m [PMID: 30199704]	Inhibition	6.05	pIC50
zileuton	Inhibition	5.82	pIC50
honokiol	Inhibition	5.38	pIC50

Binding affinities (BindingDB)

132 measured of 182 human assays (186 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-Furan-3-yl-7-[6-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-pyridin-2-ylmethoxy]-naphthalene-2-carbonitrile	IC50	20 nM
2-{Adamantan-2-yl-[4-(quinolin-2-ylmethoxy)-phenyl]-methoxyimino}-propionic acid	IC50	20 nM
{Adamantan-2-yl-[4-(quinolin-2-ylmethoxy)-phenyl]-methoxyimino}-acetic acid	IC50	21 nM
(1S,2S or 1R,2R)-N-(3-Cyano-1-methyl- 1H-pyrazol-4-yl)-2-[4-(3-methyl-1H- pyrazol-5- yl)benzoyl]cyclohexanecarboxamide	IC50	22 nM	US-10183947: Pyrazole derivatives useful as 5-lipoxygenase activating protein (FLAP) inhibitors
N-aryl-4-aryl-1,3-thiazole-2-amine, 6	IC50	25 nM
7-[3-Fluoro-5-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-phenoxymethyl]-4-furan-3-yl-quinoline-2-carbonitrile	IC50	27 nM
(1R,2R or 1S,2S)-N-(5-Cyano-1-methyl- 1H-pyrazol-4-yl)-2-[4-(1H-pyrazol-3- yl)benzoyl]cyclohexanecarboxamide	IC50	28 nM	US-10183947: Pyrazole derivatives useful as 5-lipoxygenase activating protein (FLAP) inhibitors
CHEMBL3099680	IC50	30 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11m	IC50	31 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 5	IC50	35 nM
4-Furan-3-yl-7-[6-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-pyridin-2-ylmethoxy]-quinoline-2-carbonitrile	IC50	36 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11k	IC50	45 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11n	IC50	49 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 31	IC50	60 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 15	IC50	63 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 8	IC50	65 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11l	IC50	67 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 32	IC50	70 nM
4-Furan-3-yl-7-[6-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-pyridin-2-yloxymethyl]-naphthalene-2-carbonitrile	IC50	80 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 7	IC50	81 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 4	IC50	82 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11c	IC50	84 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 12	IC50	85 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11a	IC50	86 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 11	IC50	92 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 28	IC50	92 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 16	IC50	93 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11g	IC50	95 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11e	IC50	96 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11b	IC50	97 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 3	IC50	99 nM
1-Benzyl-4-furan-3-yl-7-[6-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-pyridin-2-ylmethoxy]-1H-quinolin-2-one	IC50	102 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 17	IC50	104 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 25	IC50	105 nM
4131JH0380	IC50	110 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 24	IC50	120 nM
7-[3-Fluoro-5-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-phenylsulfanylmethyl]-4-furan-3-yl-quinoline-2-carbonitrile	IC50	124 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 14	IC50	127 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11h	IC50	130 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11o	IC50	130 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11q	IC50	130 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11d	IC50	140 nM
4-Furan-3-yl-7-[3-(3-hydroxy-6,8-dioxa-bicyclo[3.2.1]oct-3-yl)-benzyloxy]-3H-naphtho[2,3-c]furan-1-one	IC50	140 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 9	IC50	140 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 13	IC50	146 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11f	IC50	150 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11i	IC50	150 nM
CHEMBL2029840	IC50	150 nM
N-aryl-4-aryl-1,3-thiazole-2-amine, 27	IC50	160 nM
5-hydroxy-1H-benzo[g]indole-3-carboxylate, 11r	IC50	170 nM

ChEMBL bioactivities

3322 potent at pChembl≥5 of 3600 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	CHEMBL377821
9.30	IC50	0.5	nM	CHEMBL205800
9.10	IC50	0.8	nM	CHEMBL377094
9.05	IC50	0.9	nM	CHEMBL204365
8.80	IC50	1.6	nM	QUIFLAPON
8.72	IC50	1.9	nM	CHEMBL205189
8.64	IC50	2.3	nM	CHEMBL207057
8.57	IC50	2.7	nM	CHEMBL205222
8.52	IC50	3	nM	CHEMBL50170
8.52	IC50	3	nM	CHEMBL81812
8.52	IC50	3	nM	CHEMBL423638
8.52	EC50	3	nM	CHEMBL194522
8.52	IC50	3	nM	CHEMBL207109
8.43	IC50	3.7	nM	CHEMBL204633
8.43	IC50	3.7	nM	CHEMBL204781
8.41	IC50	3.9	nM	CHEMBL5751506
8.40	IC50	4	nM	CHEMBL3238463
8.37	IC50	4.3	nM	CHEMBL206632
8.32	IC50	4.8	nM	CHEMBL5756454
8.22	IC50	6	nM	CHEMBL3238207
8.20	IC50	6.3	nM	CHEMBL4542281
8.15	IC50	7	nM	CHEMBL32842
8.15	IC50	7	nM	CHEMBL5398068
8.15	IC50	7	nM	CHEMBL5421129
8.15	IC50	7	nM	CHEMBL280055
8.10	IC50	8	nM	QUIFLAPON SODIUM
8.10	IC50	8	nM	CHEMBL2093045
8.10	IC50	8	nM	CHEMBL275634
8.10	IC50	8	nM	CHEMBL275887
8.10	IC50	8	nM	CHEMBL3113612
8.10	IC50	8	nM	CHEMBL5395696
8.10	IC50	7.9	nM	CHEMBL1290649
8.09	IC50	8.1	nM	CHEMBL5996786
8.08	Ki	8.4	nM	CHEMBL3113617
8.07	IC50	8.6	nM	CHEMBL3113617
8.07	IC50	8.6	nM	CHEMBL5747103
8.05	IC50	9	nM	CHEMBL349526
8.05	IC50	9	nM	CHEMBL377094
8.05	IC50	9	nM	CHEMBL5789235
8.02	Ki	9.5	nM	CHEMBL3113612
8.01	IC50	9.7	nM	CHEMBL3113612
8.00	IC50	10	nM	CHEMBL159516
8.00	IC50	10	nM	CHEMBL159297
8.00	IC50	10	nM	CHEMBL129970
8.00	Ki	9.9	nM	CHEMBL3113618
8.00	IC50	10	nM	CHEMBL3113618
8.00	IC50	10	nM	CHEMBL3238465
8.00	IC50	10	nM	CHEMBL3353726
8.00	IC50	10	nM	CHEMBL5413117
8.00	IC50	10	nM	CHEMBL5401317

PubChem BioAssay actives

2819 with measured affinity, of 6100 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
6-[3-fluoro-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]sulfanyl-4-(4-fluorophenyl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0005	uM
7-[3-fluoro-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]sulfanyl-4-phenylchromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0005	uM
7-[3-fluoro-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]sulfanyl-4-(furan-3-yl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0008	uM
3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	1067164: Inhibition of 5-LOX (unknown origin) using arachidonic acid as substrate after 5 mins by EIA	ic50	0.0016	uM
7-[[3-fluoro-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenoxy]methyl]-4-(4-fluorophenyl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0019	uM
7-[[3-fluoro-5-[(1S,3S,5R)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl]phenoxy]methyl]-4-(furan-3-yl)quinoline-2-carbonitrile	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0023	uM
7-[[3-fluoro-5-[1-hydroxy-1-(1,3-thiazol-2-yl)propyl]phenoxy]methyl]-4-(4-fluorophenyl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0027	uM
3-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]-1-(4-methylsulfonylphenyl)-5-phenylpyrazole	254738: Inhibitory concentration against arachidonate 5-lipoxygenase	ic50	0.0030	uM
3-[2-[(4-chlorophenyl)methyl]-6-methyl-9-(quinolin-2-ylmethoxy)-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraen-3-yl]-2,2-dimethylpropanoic acid	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0030	uM
7-[[3-fluoro-5-[(1S,3S,5R)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl]phenoxy]methyl]-4-(furan-3-yl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0030	uM
2-[(4-chlorophenyl)methyl]-3-[2,2-dimethyl-3-(2H-tetrazol-5-yl)propyl]-6-methyl-9-[2-(5-phenyl-2-pyridinyl)ethyl]-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraene	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0030	uM
(5S,6Z,8E,10E,12R,14Z)-20,20,20-trifluoro-5,12-dihydroxyicosa-6,8,10,14-tetraenoic acid	254621: Effective concentration required to inhibit 5-lipoxygenase by 50%	ec50	0.0030	uM
7-[[3-fluoro-5-[(1S,3S,5R)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl]phenoxy]methyl]-4-phenylchromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0037	uM
7-[[3-fluoro-5-(1-hydroxy-1-pyridin-2-ylpropyl)phenoxy]methyl]-4-(furan-3-yl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0037	uM
N-naphthalen-1-yl-3,5-dinitrobenzamide	1126817: Inhibition of human 5-LOX using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition by H2DCFDA staining-based fluorometric analysis	ic50	0.0040	uM
4-(4-chlorophenyl)-7-[3-fluoro-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]sulfanylchromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0043	uM
(3-methylphenyl) 3,5-dinitrobenzoate	1126817: Inhibition of human 5-LOX using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition by H2DCFDA staining-based fluorometric analysis	ic50	0.0060	uM
7-fluoro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-1-benzofuran-4-ol	160519: Concentration required for 50 % inhibition of leukotriene B4 production in human PMN compared with controls in the absence of compound	ic50	0.0070	uM
4-dibenzothiophen-4-ylbenzene-1,2-diol	2001565: Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 5 to 10 mins with compound followed by substrate addition and measured after 10 mins by HPLC analysis	ic50	0.0070	uM
4-naphthalen-2-ylbenzene-1,2-diol	2001565: Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 5 to 10 mins with compound followed by substrate addition and measured after 10 mins by HPLC analysis	ic50	0.0070	uM
methyl 3-phenyl-6-[[4-(1,1,1-trifluoro-2-hydroxybutan-2-yl)triazol-1-yl]methyl]-1-benzothiophene-2-carboxylate	538874: Inhibition of human recombinant 5-lipoxygenase assessed as arachidonic acid oxidation	ic50	0.0079	uM
2-[(4-chlorophenyl)methyl]-3-[2,2-dimethyl-3-(2H-tetrazol-5-yl)propyl]-6-methyl-9-[(5-phenyl-2-pyridinyl)methoxy]-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraene	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0080	uM
4-(5a,9a-dihydrothianthren-1-yl)benzene-1,2-diol	2001565: Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 5 to 10 mins with compound followed by substrate addition and measured after 10 mins by HPLC analysis	ic50	0.0080	uM
sodium 3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0080	uM
(2E)-2-[4-(4-fluorophenyl)-1-[4-(quinolin-2-ylmethoxy)phenyl]butoxy]iminopropanoic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0090	uM
2-[(E)-1-[4-[4-[(4S)-2,2,4-trimethyl-1,3-dioxolan-4-yl]thiophen-2-yl]sulfanylphenyl]ethylideneamino]oxyacetonitrile	92721: Inhibition of LT biosynthesis in vitro using A-23187-stimulated human whole blood.	ic50	0.0100	uM
4-anthracen-9-ylbenzene-1,2-diol	2001565: Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 5 to 10 mins with compound followed by substrate addition and measured after 10 mins by HPLC analysis	ic50	0.0100	uM
(2E)-2-[3-methyl-3-phenyl-1-[4-(quinolin-2-ylmethoxy)phenyl]butoxy]iminoacetic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0100	uM
(2E)-2-[2-butyl-1-[4-(quinolin-2-ylmethoxy)phenyl]hexoxy]iminoacetic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0100	uM
2-(4-chlorophenyl)-5-(4-methoxyphenyl)-1,3-thiazol-4-ol	1174544: Inhibition of 5-LO in human PMNL using arachidonic acid as substrate assessed as product formation incubated for 15 mins prior to substrate addition measured after 10 mins by HPLC analysis	ic50	0.0100	uM
4-methoxy-4-[3-(naphthalen-2-ylmethoxy)phenyl]oxane	6709: In vitro potency against human 5-Lipoxygenase	ic50	0.0100	uM
4-(2-ethoxynaphthalen-1-yl)benzene-1,2-diol	2001565: Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 5 to 10 mins with compound followed by substrate addition and measured after 10 mins by HPLC analysis	ic50	0.0100	uM
N-(3-methylphenyl)-3,5-dinitrobenzamide	1126817: Inhibition of human 5-LOX using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition by H2DCFDA staining-based fluorometric analysis	ic50	0.0100	uM
7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-1-benzofuran-4-ol	160519: Concentration required for 50 % inhibition of leukotriene B4 production in human PMN compared with controls in the absence of compound	ic50	0.0110	uM
4-[2-[(4-chlorophenyl)methyl]-6-methyl-9-[(5-phenyl-2-pyridinyl)methoxy]-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraen-3-yl]-3,3-dimethyl-N-methylsulfonylbutanamide	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0110	uM
1-[3-phenyl-6-[[4-(1,1,1-trifluoro-2-hydroxybutan-2-yl)triazol-1-yl]methyl]-1-benzothiophen-2-yl]ethanone	538874: Inhibition of human recombinant 5-lipoxygenase assessed as arachidonic acid oxidation	ic50	0.0110	uM
2-[(4-chlorophenyl)methyl]-3-[2,2-dimethyl-3-(2H-tetrazol-5-yl)propyl]-6-methyl-9-[(5-phenyl-2-pyridinyl)methylsulfanyl]-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraene	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0110	uM
7-[[3-fluoro-5-[(1S,3S,5R)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl]phenoxy]methyl]-4-(4-fluorophenyl)chromen-2-one	264153: Inhibition of LTB4 production in calcium ionophore A-23187-stimulated human polymorphonuclear leukocyte	ic50	0.0116	uM
2-[(4-methoxyphenyl)methyl]-3,7-dimethyl-5-propyl-1-benzofuran-4-ol	160519: Concentration required for 50 % inhibition of leukotriene B4 production in human PMN compared with controls in the absence of compound	ic50	0.0120	uM
3-[2-[(4-chlorophenyl)methyl]-9-[(5-methoxy-2-pyridinyl)methoxy]-6-methyl-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraen-3-yl]-2,2-dimethylpropanoic acid	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0120	uM
4-[2-[(4-chlorophenyl)methyl]-6-methyl-9-[(5-phenyl-2-pyridinyl)methoxy]-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraen-3-yl]-3,3-dimethylbutanoic acid	93436: In vitro inhibition of LTB4 biosynthesis in [Ca(2+)]-ionophore-activated human polymorphonuclear leukocytes	ic50	0.0120	uM
(2E)-2-[cycloheptyl-[4-(quinolin-2-ylmethoxy)phenyl]methoxy]iminopropanoic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0130	uM
4-[(E)-2-[3-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-1H-pyrazol-5-yl]ethenyl]-2-methoxyphenol	1155590: Inhibition of 5-LO-mediated LTB4 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
4-[(E)-2-[3-(4-hydroxy-3-methoxyphenyl)-1H-pyrazol-5-yl]ethenyl]-2-methoxyphenol	1155590: Inhibition of 5-LO-mediated LTB4 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
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	1155590: Inhibition of 5-LO-mediated LTB4 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
7-chloro-2-[(2,4-dimethoxyphenyl)methyl]-3-methyl-5-propyl-1-benzofuran-4-ol	160519: Concentration required for 50 % inhibition of leukotriene B4 production in human PMN compared with controls in the absence of compound	ic50	0.0130	uM
N-hydroxy-N-[(E)-3-(3-phenoxyphenyl)prop-2-enyl]acetamide	1155590: Inhibition of 5-LO-mediated LTB4 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
(2E)-2-[[2-chloro-4-[(5-fluoro-1,3-benzothiazol-2-yl)methoxy]phenyl]-cyclohexylmethoxy]iminoacetic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0140	uM
(2E)-2-[[2-chloro-4-(quinolin-2-ylmethoxy)phenyl]-cyclohexylmethoxy]iminopropanoic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0140	uM
(2E)-2-[2-butyl-1-[4-(quinolin-2-ylmethoxy)phenyl]hexoxy]iminopropanoic acid	89122: Inhibition of calcium ionophore (A-23187)-stimulated LTB4 formation in human neutrophil assay	ic50	0.0140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
zileuton	affects abundance, increases reaction, affects binding, decreases activity, decreases abundance (+6 more)	22
Leukotriene B4	decreases activity, increases activity, increases expression, decreases abundance, increases reaction (+6 more)	9
Arachidonic Acid	decreases reaction, affects localization, increases expression, decreases response to substance, increases metabolic processing (+6 more)	7
Calcimycin	affects localization, decreases activity, increases abundance, decreases reaction, increases activity (+3 more)	6
Valproic Acid	affects cotreatment, increases expression, increases methylation	6
Masoprocol	decreases activity, decreases chemical synthesis, affects response to substance, decreases reaction, increases abundance (+1 more)	5
Calcitriol	increases expression, increases reaction, increases activity	4
Lipopolysaccharides	increases phosphorylation, affects response to substance, decreases expression, decreases reaction, increases expression (+2 more)	4
pirinixic acid	decreases activity	3
Benzo(a)pyrene	increases expression, increases reaction, decreases methylation, increases methylation	3
N-Formylmethionine Leucyl-Phenylalanine	increases activity, increases phosphorylation, decreases reaction, decreases activity, increases abundance (+2 more)	3
Platelet Activating Factor	increases expression, affects cotreatment, increases activity, increases phosphorylation, decreases activity (+2 more)	3
benoxaprofen	decreases activity, decreases chemical synthesis, increases abundance	2
sodium arsenite	decreases reaction, increases activity, increases phosphorylation, affects cotreatment, decreases expression	2
ochratoxin A	increases expression, increases reaction, decreases reaction, affects expression, decreases expression	2
N-(3-phenoxycinnamyl)acetohydroxamic acid	decreases activity	2
MK-886	decreases reaction, increases metabolic processing, increases expression	2
U 0126	decreases reaction, increases activity, increases phosphorylation, increases expression	2
Benzene	increases expression, affects response to substance	2
Cisplatin	affects cotreatment, increases expression	2
Hydrogen Peroxide	increases reaction, increases activity, increases chemical synthesis, decreases reaction, increases abundance	2
Nickel	increases expression	2
Nicotine	decreases reaction, increases expression, affects cotreatment	2
Sorbitol	increases phosphorylation, decreases reaction, increases activity, affects cotreatment, affects localization	2
Tetradecanoylphorbol Acetate	affects cotreatment, affects localization, decreases reaction, increases activity, increases phosphorylation	2
Tretinoin	increases expression	2
Vitamin E	decreases activity	2
Leukotriene C4	decreases reaction, increases abundance, decreases abundance, decreases activity	2
Leukotriene D4	decreases activity, increases abundance, decreases abundance	2
Leukotriene E4	decreases activity, decreases abundance	2

ChEMBL screening assays

849 unique, capped per target: 758 binding, 90 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2050900	Binding	Inhibition of 5-lipoxygenase/FLAP in calcium ionophore-stimulated human whole blood assessed as residual LTB4 level at 10 uM preincubated for 15 mins prior to calcium ionophore-stimulation measured after 15 mins by LC-MS/MS analysis	Structure-activity relationship of nonacidic quinazolinone inhibitors of human microsomal prostaglandin synthase 1 (mPGES 1). — J Med Chem
CHEMBL700005	Functional	Inhibition of calcium ionophore (A23187) stimulated LTB4 formation in human neutrophils	O-alkylcarboxylate oxime and N-hydroxyurea analogs of substituted indole leukotriene biosynthesis inhibitors — Bioorg Med Chem Lett
CHEMBL4351299	ADMET	Inhibition of 5-lipoxygenase (unknown origin)	Novel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5JG	HAP1 ALOX5 (-) 2	Cancer cell line	Male
CVCL_B5JH	HAP1 ALOX5 (-) 3	Cancer cell line	Male
CVCL_XL31	HAP1 ALOX5 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery