LTA4H

Summary

LTA4H (leukotriene A4 hydrolase, HGNC:6710) is a protein-coding gene on chromosome 12q23.1, encoding Leukotriene A-4 hydrolase (P09960). Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities.

The protein encoded by this gene is an enzyme that contains both hydrolase and aminopeptidase activities. The hydrolase activity is used in the final step of the biosynthesis of leukotriene B4, a proinflammatory mediator. The aminopeptidase activity has been shown to degrade proline-glycine-proline (PGP), a neutrophil chemoattractant and biomarker for chronic obstructive pulmonary disease (COPD). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4048 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 90 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6710
Approved symbol	LTA4H
Name	leukotriene A4 hydrolase
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111144
Ensembl biotype	protein_coding
OMIM	151570
Entrez	4048

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000228740, ENST00000413268, ENST00000537111, ENST00000547393, ENST00000547982, ENST00000548375, ENST00000548852, ENST00000552091, ENST00000552789, ENST00000553041, ENST00000852104, ENST00000852105, ENST00000852106, ENST00000852107, ENST00000852108, ENST00000920967, ENST00000920968, ENST00000920969, ENST00000961644, ENST00000961645, ENST00000961646, ENST00000961647

RefSeq mRNA: 7 — MANE Select: NM_000895 NM_000895, NM_001256643, NM_001256644, NM_001414263, NM_001414264, NM_001414265, NM_001414266

CCDS: CCDS58266, CCDS58267, CCDS9059

Canonical transcript exons

ENST00000228740 — 19 exons

Exon	Start	End
ENSE00002370169	96035361	96035587
ENSE00002379270	96000753	96001106
ENSE00003472107	96027444	96027564
ENSE00003489965	96015583	96015694
ENSE00003518654	96013188	96013258
ENSE00003522157	96017557	96017580
ENSE00003525601	96006314	96006409
ENSE00003576347	96002960	96003064
ENSE00003577329	96013750	96013853
ENSE00003633243	96021085	96021137
ENSE00003644438	96019168	96019240
ENSE00003645699	96022147	96022251
ENSE00003654590	96024479	96024547
ENSE00003665975	96018763	96018903
ENSE00003669358	96017044	96017114
ENSE00003669758	96003838	96003920
ENSE00003678583	96014855	96014999
ENSE00003685086	96029055	96029185
ENSE00003689835	96009094	96009148

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.0859 / max 3041.2725, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132765	86.9852	1819
132766	12.0964	1779
132764	0.0043	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.42	gold quality
mononuclear cell	CL:0000842	99.39	gold quality
leukocyte	CL:0000738	99.36	gold quality
granulocyte	CL:0000094	99.12	gold quality
visceral pleura	UBERON:0002401	99.09	gold quality
trabecular bone tissue	UBERON:0002483	98.81	gold quality
bone marrow	UBERON:0002371	98.78	gold quality
esophagus squamous epithelium	UBERON:0006920	98.75	gold quality
epithelium of esophagus	UBERON:0001976	98.72	gold quality
germinal epithelium of ovary	UBERON:0001304	98.55	gold quality
secondary oocyte	CL:0000655	98.31	gold quality
lower lobe of lung	UBERON:0008949	98.28	gold quality
oocyte	CL:0000023	98.25	gold quality
blood	UBERON:0000178	98.18	gold quality
bone marrow cell	CL:0002092	98.10	gold quality
pleura	UBERON:0000977	98.07	gold quality
lung	UBERON:0002048	98.02	gold quality
squamous epithelium	UBERON:0006914	97.99	gold quality
right lung	UBERON:0002167	97.94	gold quality
esophagus mucosa	UBERON:0002469	97.73	gold quality
oral cavity	UBERON:0000167	97.72	gold quality
tongue squamous epithelium	UBERON:0006919	97.71	gold quality
upper lobe of lung	UBERON:0008948	97.58	gold quality
left ovary	UBERON:0002119	97.57	gold quality
upper lobe of left lung	UBERON:0008952	97.53	gold quality
parietal pleura	UBERON:0002400	97.52	gold quality
ovary	UBERON:0000992	97.28	gold quality
duodenum	UBERON:0002114	97.28	gold quality
lower esophagus mucosa	UBERON:0035834	97.28	gold quality
gingiva	UBERON:0001828	97.21	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	800.93
E-MTAB-6701	yes	29.89
E-MTAB-6678	yes	26.21
E-CURD-112	yes	22.28
E-GEOD-130148	yes	20.98
E-GEOD-125970	yes	14.65
E-MTAB-9801	yes	8.05
E-GEOD-70580	no	1487.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

18 targeting LTA4H, 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-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-216B-5P	97.16	66.76	1126

Literature-anchored findings (GeneRIF, showing 38)

• 5-lipoxygenase and leukotriene A4 hydrolase expression in atherosclerotic lesions correlates with symptoms of plaque instability (PMID:16698924)
• leukotriene A4 hydrolase These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility (PMID:18547289)
• Analysis of the thermodynamic parameters of irreversible thermal unfolding suggests that entropy-driven factors are responsible for the fast unfolding rate of the cold-adapted aminopeptidase. (PMID:18599387)
• The 5-lipoxygenase-leukotriene A4 pathway might play roles in the proliferation of human glioma cells. (PMID:19919819)
• Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations. (PMID:20067482)
• In humans, protection from both tuberculosis and multibacillary leprosy is associated with heterozygosity for LTA4H polymorphisms that have previously been correlated with differential LTB(4) production. (PMID:20211140)
• Several point mutants of LTA4H with altered substrate specificities were designed. (PMID:20432426)
• LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma. (PMID:20810156)
• common polymorphisms in the LTA4H gene do not play any major role in susceptibility to clinical pulmonary tuberculosis (PMID:21112816)
• It was found modest association with LTA4H rs1978331C (intron 11) with increased FEV1 (p = 0.029) and with increased FEV1/FVC ratio (p = 0.020). (PMID:22206291)
• Structural origins for the loss of catalytic activities of bifunctional human LTA4H revealed through molecular dynamics simulations. (PMID:22848428)
• genetic association studies in population of Han Chinese in Eastern China: Using a recessive genetic model, an SNP in LTA4H (rs6538697) is associated with increased risk of ischemic stroke. (PMID:23079278)
• We identified a novel leukotriene haplotype that appears to be protective toward subclinical atherosclerosis. This association is modified by dietary intake of polyunsaturated fatty acids (PMID:23153620)
• Data indicate that 13S,14S-epoxy-docosahexaenoic acid (DHA) inhibits leukotriene B4 (LTB4) biosynthesis by leukotriene A4 hydrolase (LTA4H). (PMID:23504711)
• The LTA4H A-9188>G polymorphism has a strong association with severe asthma in children. (PMID:23573270)
• The results of our study failed to confirm whether the selected variants in LTA4H gene within the LT metabolism pathway contribute to platelet reactivity in a diabetic population treated with ASA. (PMID:23828562)
• The best proteinogenic amino acid recognized by LTA4H is arginine. (PMID:24573245)
• Report no association between LTA4H SNPs and atherosclerotic plaque phenotypes. (PMID:25721704)
• LTA4H promoter region SNP was associated with susceptibility to bacteriologically confirmed bacterial meningitis but did not influence clinical presentation, disease severity or survival following dexamethasone treatment. (PMID:25799317)
• A higher incidence of severe IRIS among patients with mutant LTA4H genotypes (CT and TT) was observed compared to the wild type, despite similar IRIS incidence and immune restoration in both groups. Steroids were effective in alleviating IRIS in all the genotypes (PMID:27643598)
• The LTA4H promoter polymorphism correlated with CSF mononuclear cell count but not with mortality in tuberculous meningitis (PMID:28419315)
• LTA4H genotype predicted survival of HIV-uninfected patients, with TT-genotype patients significantly more likely to survive tuberculous meningitis than CC-genotype patients. LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from tuberculous meningitis. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals. (PMID:28419368)
• The structures reveal that a single catalytic water is involved in both catalytic activities of LTA4H, alternating between epoxide ring opening and peptide bond hydrolysis, assisted by E271 and E296, respectively. Moreover, we have found two conformations of LTA4H, uncovering significant domain movements. (PMID:28827365)
• LTA4H is the major Pro-Gly-Pro degrading enzyme in human blood. (PMID:29051536)
• the current study demonstrates the ability of eosinophils to express LTA4H and generate LTB4 in response to their activation. Eosinophil derived LTB4 likely contributes to the presence and severity of inflammation in asthma, in particular, those presentations characterized by prominent eosinophilia (and a paucity of neutrophils). (PMID:30352167)
• We found no convincing association between SNPs in ALOX5 (rs12264801) or LTA4H (rs2072512 and rs2540477) and myocardial infarction (PMID:30678701)
• Gliotoxin suppresses the biosynthesis of the potent neutrophil chemoattractant LTB4 by direct interference with LTA4H thereby impairing neutrophil functions in invasive aspergillosis. (PMID:30745237)
• Low LTA4H expression is associated with antidiastole of tuberculous pleural effusion. (PMID:30791695)
• The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn’s disease instead of intestinal tuberculosis. (PMID:31093505)
• the identification of FSCN1-binding partners enhances understanding of the mechanism of FSCN1-mediated malignant phenotypes, and these findings indicate that FSCN1 binds to AIMP1 and LTA4H might promote the progression of laryngeal squamous cell carcinoma . (PMID:31287215)
• Identification of Human Leukotriene A4 Hydrolase Inhibitors Using Structure-Based Pharmacophore Modeling and Molecular Docking. (PMID:32580506)
• Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy. (PMID:33329520)
• LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis. (PMID:34595756)
• Clinical Implications of LTA4H Genetic Polymorphism in Patients with Chronic Obstructive Pulmonary Disease. (PMID:34694182)
• Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis. (PMID:36879040)
• LTA4H extensively associates with mRNAs and lncRNAs indicative of its novel regulatory targets. (PMID:36923505)
• Inhibition of Leukotriene A4 Hydrolase Suppressed Cartilage Degradation and Synovial Inflammation in a Mouse Model of Experimental Osteoarthritis. (PMID:37086004)
• Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin. (PMID:38300441)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lta4h	ENSDARG00000006029
mus_musculus	Lta4h	ENSMUSG00000015889
rattus_norvegicus	Lta4h	ENSRNOG00000004494
drosophila_melanogaster	CG10602	FBGN0032721
caenorhabditis_elegans		WBGENE00016589

Paralogs (11): TRHDE (ENSG00000072657), LNPEP (ENSG00000113441), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), AOPEP (ENSG00000148120), ERAP1 (ENSG00000164307), ERAP2 (ENSG00000164308), ANPEP (ENSG00000166825), LVRN (ENSG00000172901), RNPEP (ENSG00000176393)

Protein

Protein identifiers

Leukotriene A-4 hydrolase — P09960 (reviewed: P09960)

Alternative names: Leukotriene A(4) hydrolase, Tripeptide aminopeptidase LTA4H

All UniProt accessions (3): P09960, A0A140VK27, B4DEH5

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4). Can utilize LTA5 less effectively as a substrate than LTA4, and produce LTB5. Also has aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides. In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Tissue specificity. Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.

Post-translational modifications. Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity.

Activity regulation. Inhibited by bestatin. The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379. 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity.

Cofactor. Binds 1 zinc ion per subunit.

Pathway. Lipid metabolism; leukotriene B4 biosynthesis.

Similarity. Belongs to the peptidase M1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P09960-1	1, L-LTA4	yes
P09960-2	2, S-LTA4
P09960-3	3
P09960-4	4

RefSeq proteins (7): NP_000886, NP_001243572, NP_001243573, NP_001401192, NP_001401193, NP_001401194, NP_001401195 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001930	Peptidase_M1	Family
IPR012777	LTA4H	Family
IPR014782	Peptidase_M1_dom	Domain
IPR015211	Peptidase_M1_C	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR034015	M1_LTA4H	Family
IPR038502	M1_LTA-4_hydro/amino_C_sf	Homologous_superfamily
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR045357	Aminopeptidase_N-like_N	Domain
IPR049980	LTA4H_cat	Domain

Pfam: PF01433, PF09127, PF17900

Enzyme classification (BRENDA):

• EC 3.3.2.6 — leukotriene-A4 hydrolase (BRENDA: 11 organisms, 64 substrates, 539 inhibitors, 74 Km, 62 kcat entries)
• EC 3.4.11.6 — aminopeptidase B (BRENDA: 35 organisms, 222 substrates, 305 inhibitors, 95 Km, 61 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-ARG-2-NAPHTHYLAMIDE	—	22
LEUKOTRIENE A4	0.0027–0.06	15
L-ALANINE 2-NAPHTHYLAMIDE	0.31–1.78	6
L-ARGININE 2-NAPHTHYLAMIDE	0.137–0.587	6
L-LEUCINE 2-NAPHTHYLAMIDE	0.105–0.771	6
L-METHIONINE 2-NAPHTHYLAMIDE	0.128–0.7	6
L-LYS-2-NAPHTHYLAMIDE	0.0001–0.333	6
L-LEUCINE-4-NITROANILIDE	0.15–2.1	5
ARG-7-AMIDO-4-METHYLCOUMARIN	0.0159–0.603	5
L-ARG-7-AMIDO-4-METHYLCOUMARIN	0.048–0.208	5
L-ALANINE-4-NITROANILIDE	0.0009–10.8	4
L-ISOLEUCINE 2-NAPHTHYLAMIDE	0.488–0.698	4
L-VALINE 2-NAPHTHYLAMIDE	0.235–0.808	4
L-ARG-BETA-NAPHTHYLAMIDE	0.0026–0.3	4
L-ALA-P-NITROANILIDE	1.9–3	3

Catalyzed reactions (Rhea), 4 shown:

• leukotriene A4 + H2O = leukotriene B4 (RHEA:22324)
• (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O = resolvin E1 (RHEA:50272)
• (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O = 18S-resolvin E1 (RHEA:51988)
• leukotriene A5 + H2O = leukotriene B5 (RHEA:85599)

UniProt features (120 total): helix 32, mutagenesis site 27, strand 25, turn 8, binding site 6, modified residue 5, sequence conflict 5, site 4, splice variant 3, active site 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

77 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3U9W	X-RAY DIFFRACTION	1.25
8AVA	X-RAY DIFFRACTION	1.35
8AWH	X-RAY DIFFRACTION	1.42
3B7S	X-RAY DIFFRACTION	1.47
5NI2	X-RAY DIFFRACTION	1.5
5NI6	X-RAY DIFFRACTION	1.54
5NID	X-RAY DIFFRACTION	1.57
3FUN	X-RAY DIFFRACTION	1.58
8QQ4	X-RAY DIFFRACTION	1.6
4MKT	X-RAY DIFFRACTION	1.62
3FH5	X-RAY DIFFRACTION	1.63
4L2L	X-RAY DIFFRACTION	1.65
4R7L	X-RAY DIFFRACTION	1.66
3FH8	X-RAY DIFFRACTION	1.67
3FTV	X-RAY DIFFRACTION	1.7
4MS6	X-RAY DIFFRACTION	1.72
5NIA	X-RAY DIFFRACTION	1.76
7AV1	X-RAY DIFFRACTION	1.79
2VJ8	X-RAY DIFFRACTION	1.8
3CHO	X-RAY DIFFRACTION	1.8
3FU0	X-RAY DIFFRACTION	1.8
3FUH	X-RAY DIFFRACTION	1.8
3B7R	X-RAY DIFFRACTION	1.81
6ENB	X-RAY DIFFRACTION	1.84
3FTW	X-RAY DIFFRACTION	1.85
8RX3	X-RAY DIFFRACTION	1.85
8RX7	X-RAY DIFFRACTION	1.85
5AEN	X-RAY DIFFRACTION	1.86
2R59	X-RAY DIFFRACTION	1.89
5NI4	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09960-F1	96.35	0.95

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 (6): 272 (pro-gly-pro binding); 376 (essential for epoxide hydrolase activity, but not for aminopeptidase activity); 379 (covalently modified during suicide inhibition by leukotrienes); 563 (pro-gly-pro binding); 297 (proton acceptor); 384 (proton donor)

Ligand- & substrate-binding residues (6): 135–137; 267–272; 296; 300; 319; 564–566

Post-translational modifications (5): 73, 337, 414, 416, 573

Mutagenesis-validated functional residues (27):

Position	Phenotype
135	srongly increased epoxide hydrolase activity.
135	strongly reduced aminopeptidase activity. strongly decreased affinity for leukotriene. abolishes epoxide hydrolase activ
137	no loss of activity.
137	aminopeptidase activity strongly impaired, but keeps lta4 activity.
137	aminopeptidase activity almost absent, but keeps lta4 activity.
140	aminopeptidase activity almost absent, but keeps lta4 activity.
269	no loss of activity.
270	no loss of activity.
271	no loss of activity.
272	complete loss of epoxide hydrolase activity and aminopeptidase activity.
272	loss of lta4 hydrolase activity, and aminopeptidase activity strongly impaired.
273	no loss of epoxide hydrolase activity and aminopeptidase activity.
296	complete loss of lta4 hydrolase and peptidase enzyme activities.
297	loss of epoxide hydrolase and aminopeptidase activities.
297	loss of aminopeptidase activity, but keeps lta4 hydrolase activity.
300	complete loss of lta4 hydrolase and peptidase enzyme activities.
319	complete loss of lta4 hydrolase and peptidase enzyme activities.
372	no loss of activity.
374	no loss of activity.
376	strongly reduced hydrolysis of peptides starting with arg. small effect on hydrolysis of peptides starting with ala. abo
376	strongly reduced aminopeptidase activity. abolishes epoxide hydrolase activity.
376	abolishes aminopeptidase activity. decreased epoxide hydrolase activity.
385	reduced aminopeptidase activity. minor effect on epoxide hydrolase activity.
564	abolishes epoxide hydrolase activity. reduced aminopeptidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-6798695	Neutrophil degranulation
R-HSA-9018676	Biosynthesis of D-series resolvins
R-HSA-9018681	Biosynthesis of protectins
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-1430728	Metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2142753	Arachidonate metabolism
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

MSigDB gene sets: 320 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ZINC_ION, GOMF_METALLOPEPTIDASE_ACTIVITY, GOCC_SECRETORY_GRANULE, GOBP_LUNG_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, HSIAO_HOUSEKEEPING_GENES, GNF2_LYN, GOBP_LEUKOTRIENE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_METAL_ION

GO Biological Process (9): proteolysis (GO:0006508), lipid metabolic process (GO:0006629), response to zinc ion (GO:0010043), leukotriene biosynthetic process (GO:0019370), peptide catabolic process (GO:0043171), response to peptide hormone (GO:0043434), type I pneumocyte differentiation (GO:0060509), leukotriene metabolic process (GO:0006691), protein metabolic process (GO:0019538)

GO Molecular Function (12): RNA binding (GO:0003723), aminopeptidase activity (GO:0004177), epoxide hydrolase activity (GO:0004301), leukotriene-A4 hydrolase activity (GO:0004463), peptidase activity (GO:0008233), zinc ion binding (GO:0008270), tripeptide aminopeptidase activity (GO:0045148), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (8): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Biosynthesis of DHA-derived SPMs	3
Biosynthesis of EPA-derived SPMs	2
Metabolism of lipids	2
Biosynthesis of specialized proresolving mediators (SPMs)	2
Arachidonate metabolism	1
Innate Immune System	1
Immune System	1
Fatty acid metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
primary metabolic process	2
ether hydrolase activity	2
aminopeptidase activity	2
intracellular organelle lumen	2
protein metabolic process	1
response to metal ion	1
leukotriene metabolic process	1
icosanoid biosynthetic process	1
peptide metabolic process	1
catabolic process	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
lung epithelial cell differentiation	1
icosanoid metabolic process	1
macromolecule metabolic process	1
nucleic acid binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
tripeptidase activity	1
metalloexopeptidase activity	1
binding	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1925 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LTA4H	ALOX5AP	P20292	950
LTA4H	LTC4S	Q16873	931
LTA4H	ALOX5	P09917	925
LTA4H	LTB4R2	Q9NPC1	892
LTA4H	LTB4R	Q15722	843
LTA4H	PLA2G2A	P14555	745
LTA4H	CYSLTR1	Q9Y271	694
LTA4H	COTL1	Q14019	674
LTA4H	CYSLTR2	Q9NS75	668
LTA4H	PLA2G4A	P47712	620
LTA4H	IL4I1	Q96RQ9	601
LTA4H	CRISP1	P54107	599
LTA4H	ALOX15	P16050	592
LTA4H	CRISP2	P16562	589
LTA4H	ABCC1	P33527	576

IntAct

31 interactions, top by confidence:

A	B	Type	Score
LTA4H	TINF2	psi-mi:“MI:0915”(physical association)	0.510
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CIAO1	SOX1	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
UBA5	PGK1	psi-mi:“MI:0914”(association)	0.350
DDA1	PGK1	psi-mi:“MI:0914”(association)	0.350
	KRAS	psi-mi:“MI:0914”(association)	0.350
CDKN2A	NHERF1	psi-mi:“MI:0914”(association)	0.350
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
OCA2	PSMD11	psi-mi:“MI:0914”(association)	0.350
SLC41A1	FADS2	psi-mi:“MI:0914”(association)	0.350
HLA-C	LTA4H	psi-mi:“MI:0915”(physical association)	0.000
MCC	LTA4H	psi-mi:“MI:0915”(physical association)	0.000
HLA-B	LTA4H	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	LTA4H	psi-mi:“MI:0915”(physical association)	0.000
GH1	LTA4H	psi-mi:“MI:0915”(physical association)	0.000
LTA4H	TINF2	psi-mi:“MI:0915”(physical association)	0.000
LTA4H		psi-mi:“MI:0915”(physical association)	0.000
LTA4H	TMEM62	psi-mi:“MI:0915”(physical association)	0.000
ARPC3	LTA4H	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (75): LTA4H (Co-fractionation), LTA4H (Co-fractionation), LTA4H (Co-fractionation), LTA4H (Co-fractionation), LTA4H (Co-fractionation), LTA4H (Co-fractionation), LTA4H (Co-fractionation), LTA4H (Co-fractionation), NAPRT (Co-fractionation), TAGLN2 (Co-fractionation), LTA4H (Affinity Capture-MS), LTA4H (Synthetic Growth Defect), LTA4H (Affinity Capture-MS), LTA4H (Affinity Capture-MS), LTA4H (Affinity Capture-MS)

ESM2 similar proteins: A1CSI2, A1DG68, A2QKF8, A3LQI7, A3LRX6, A4QUC1, A5DGF3, A5DME6, A5DSS4, A6RCT2, A6SAG8, A6ZS33, A7EJL9, A7THG7, B7EA73, G5EFT4, O94544, P09960, P19602, P24527, P30349, P32454, P37898, P52922, P55786, Q0CFY9, Q0J5V5, Q0U653, Q10740, Q11011, Q1DVD1, Q2GY21, Q2TZ99, Q3SZH7, Q4TT88, Q4X265, Q59NB8, Q5B0W8, Q6BW21, Q6C3E5

Diamond homologs: A1CSI2, A1DG68, A2QKF8, A3LQI7, A3LRX6, A4QUC1, A5DGF3, A5DME6, A5DSS4, A6QPT7, A6RCT2, A6SAG8, A6ZS33, A7EJL9, A7THG7, G5E872, G5EFT4, O09175, O94544, P09960, P19602, P24527, P30349, P52922, Q0CFY9, Q0U653, Q10736, Q10740, Q1DVD1, Q2GY21, Q2TZ99, Q3SZH7, Q4X265, Q59NB8, Q5B0W8, Q6BW21, Q6C3E5, Q6CLD3, Q6FTM0, Q6IP81

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2511 predictions. Top by Δscore:

Variant	Effect	Δscore
12:96002913:T:TA	donor_gain	1.0000
12:96002954:TCTTA:T	donor_loss	1.0000
12:96002955:CTTAC:C	donor_loss	1.0000
12:96002956:TTACT:T	donor_loss	1.0000
12:96002957:TACTT:T	donor_loss	1.0000
12:96002958:A:AC	donor_gain	1.0000
12:96002958:ACTTG:A	donor_loss	1.0000
12:96002959:C:CT	donor_gain	1.0000
12:96002959:C:G	donor_loss	1.0000
12:96002959:CTTGA:C	donor_gain	1.0000
12:96002989:T:TA	donor_gain	1.0000
12:96003060:GCCAT:G	acceptor_gain	1.0000
12:96003061:CCAT:C	acceptor_gain	1.0000
12:96003061:CCATC:C	acceptor_gain	1.0000
12:96003062:CAT:C	acceptor_gain	1.0000
12:96003062:CATC:C	acceptor_gain	1.0000
12:96003063:AT:A	acceptor_gain	1.0000
12:96003064:TCTAA:T	acceptor_loss	1.0000
12:96003065:C:CC	acceptor_gain	1.0000
12:96003066:T:C	acceptor_loss	1.0000
12:96003076:A:C	acceptor_gain	1.0000
12:96003078:T:C	acceptor_gain	1.0000
12:96003078:T:TC	acceptor_gain	1.0000
12:96003089:A:C	acceptor_gain	1.0000
12:96006308:ACTT:A	donor_loss	1.0000
12:96006309:CTT:C	donor_loss	1.0000
12:96006310:TTACC:T	donor_loss	1.0000
12:96006311:TACCC:T	donor_loss	1.0000
12:96006312:A:AC	donor_gain	1.0000
12:96006312:A:C	donor_loss	1.0000

AlphaMissense

4000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:96017101:T:A	E297V	1.000
12:96018800:T:A	E272V	1.000
12:96015685:C:A	E319D	0.999
12:96015685:C:G	E319D	0.999
12:96015686:T:A	E319V	0.999
12:96017045:A:G	W316R	0.999
12:96017045:A:T	W316R	0.999
12:96017076:A:C	N305K	0.999
12:96017076:A:T	N305K	0.999
12:96017081:C:A	G304W	0.999
12:96017091:A:C	H300Q	0.999
12:96017091:A:T	H300Q	0.999
12:96017093:G:C	H300D	0.999
12:96017093:G:T	H300N	0.999
12:96017100:T:A	E297D	0.999
12:96017100:T:G	E297D	0.999
12:96017103:A:C	H296Q	0.999
12:96017103:A:T	H296Q	0.999
12:96017105:G:C	H296D	0.999
12:96017105:G:T	H296N	0.999
12:96018799:C:A	E272D	0.999
12:96018799:C:G	E272D	0.999
12:96018802:C:A	M271I	0.999
12:96018802:C:G	M271I	0.999
12:96018802:C:T	M271I	0.999
12:96018817:G:C	F266L	0.999
12:96018817:G:T	F266L	0.999
12:96018819:A:G	F266L	0.999
12:96027453:A:C	S134R	0.999
12:96027453:A:T	S134R	0.999

dbSNP variants (sampled 300 via entrez): RS1000078275 (12:96010791 T>C), RS1000092576 (12:96034238 C>T), RS1000140981 (12:96005249 C>T), RS1000250613 (12:96042818 G>A), RS1000280556 (12:96005035 G>A), RS1000291920 (12:96012907 T>C), RS1000372591 (12:96019650 G>A), RS1000512392 (12:96007133 G>A,C), RS1000700653 (12:96044584 A>G), RS1000712763 (12:96005464 T>C), RS1000722033 (12:96014213 C>G,T), RS1000731492 (12:96044311 C>G), RS1000876012 (12:96033144 G>C), RS1001015370 (12:96006774 T>G), RS1001108422 (12:96026115 T>G)

Disease associations

OMIM: gene MIM:151570 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000839_6	Height	3.000000e-06
GCST003786_1	Small intestine neuroendocrine tumor	3.000000e-09
GCST006585_2710	Blood protein levels	4.000000e-06
GCST007637_21	Diffusing capacity of carbon monoxide	2.000000e-06
GCST010002_220	Refractive error	1.000000e-19
GCST010653_48	Thyroid stimulating hormone levels	6.000000e-29

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009369	diffusing capacity of the lung for carbon monoxide

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4618 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 240,597 (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
CHEMBL1560	CAPTOPRIL	4	66,415
CHEMBL93	ZILEUTON	4	21,372
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL165	RESVERATROL	3	60,144
CHEMBL2103847	TOSEDOSTAT	2	328
CHEMBL26424	TESMILIFENE	2	3,376
CHEMBL29292	UBENIMEX	2	38,430
CHEMBL4297604	ACEBILUSTAT	2	171

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2660845	Efficacy	3	montelukast	Asthma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2660845	LTA4H	3	2.25	1	montelukast

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Hydrolases & Lipases

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

Ligand	Action	Affinity	Parameter
LYS006	Inhibition	8.7	pIC50
compound 1a [PMID: 25692029]	Inhibition	8.27	pKi
kelatorphan	Inhibition	8.0	pKi
DG-051	Inhibition	7.3	pIC50
acebilustat	Inhibition	7.22	pIC50
SC-22716	Inhibition	6.7	pIC50
bestatin	Inhibition	5.4	pKi

Binding affinities (BindingDB)

592 measured of 600 human assays (618 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2- yl]benzyl}piperidin-4-yl)butanoic acid	IC50	0.042 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl)urea	IC50	0.07 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
4-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl)benzoic acid	IC50	0.08 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl)methanesulfonamide	IC50	0.09 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(3S)-3-{4-[(1s,4s)-7- azabicyclo[2.2.1]hept-7- ylmethyl]phenyl}-2,3- dihydro[1,4]dioxino[2,3- b]pyridine	IC50	0.09 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{(1S,4S)-5-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-2,5-diaza- bicyclo[2.2.2]oct-2-yl}-ethanone	IC50	0.09 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
5-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-hexahydro-pyrrolo[3,4- c]pyrrole-2-carboxylic acid amide	IC50	0.09 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-2- methylpiperidine	IC50	0.1 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(3S)-3-[4-(azepan-1- ylmethyl)phenyl]-2,3- dihydro[1,4]dioxino[2,3- b]pyridine	IC50	0.1 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
4-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl)butanoic acid	IC50	0.1 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
7-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-1,7- diazaspiro[4.4]nonane-1- carboxamide	IC50	0.1 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
2-[(3R)-1-[[4-[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]phenyl]methyl]pyrrolidin-3-yl]acetic acid	IC50	0.11 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(1S,4S)-5-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-2,5-diaza- bicyclo[2.2.1]heptane-2- carboxylic acid amide	IC50	0.11 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
7-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}-1,7- diazaspiro[4.4]nonan-2-one	IC50	0.12 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2- yl]benzyl}piperidine-4-carboxylic acid	IC50	0.12 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2- yl]benzyl}piperidin-4- yl)(morpholin-4-yl)methanone	IC50	0.12 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-(1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2- yl]benzyl}pyrrolidin-3-yl)-N- methylacetamide	IC50	0.13 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-4-(1H- tetrazol-5-yl)piperidine	IC50	0.13 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(3S)-3-{4-[(3-methoxypiperidin- 1-yl)methyl]phenyl}-2,3- dihydro[1,4]dioxino[2,3- b]pyridine	IC50	0.13 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-4-(1,1- dioxido-1,2-thiazolidin-2- yl)piperidine	IC50	0.13 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
8-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}-1,3,8- triazaspiro[4.5]decane-2,4-dione	IC50	0.13 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(3R)-1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}pyrrolidin- 3-ol	IC50	0.14 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl(morpholin-4-yl)methanone	IC50	0.14 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl]piperidin-4- yl)-2-hydroxyacetamide	IC50	0.14 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
4-[(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl)methyl]benzoic acid	IC50	0.14 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{5-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-hexahydro-pyrrolo[3,4- c]pyrrol-2-yl}-ethanone	IC50	0.14 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
8-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-2,8- diazaspiro[4.5]decan-1-one	IC50	0.15 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(3S)-3-[4-(morpholin-4- ylmethyl)phenyl]-2,3- dihydro[1,4]dioxino[2,3- b]pyridine	IC50	0.15 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
3-[(4-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2- yl]benzyl}piperazin-1- yl)methyl]benzoic acid	IC50	0.15 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-{1-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-piperidin-4-yl}-2- methoxy-acetamide	IC50	0.15 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
2-{1-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-piperidin-4-yloxy}- acetamide	IC50	0.15 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
8-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}-2,8- diazaspiro[4.5]decan-1-one	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidine- 4-carboxylic acid	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidine- 4-carbonitrile	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl)piperidin-4- yl)-2-hydroxy-2- methylpropanamide	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-4- yl)-1- hydroxycyclopropanecarboxamide	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-{l-[4-(2,3-dihydro-1,4- benzodioxin-2- yl)benzyl]piperidin-4- yl}methanesulfonamide	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-N- methylpiperidine-4-carboxamide	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(1S,5R)-3-[[4-[(3S)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl]phenyl]methyl]-N-(2-hydroxy-2-methylpropyl)-3-azabicyclo[3.1.0]hexane-6-carboxamide	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
4-{1-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-piperidin-4-yl]- cyclohexanecarboxylic acid	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
[(1R,5S)-8-[[4-[(3S)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl]phenyl]methyl]-8-azabicyclo[3.2.1]octan-3-yl]urea	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{(1S,4S)-5-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-2,5-diaza- bicyclo[2.2.1]hept-2-yl}-ethanone	IC50	0.16 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}-N- methylcyclopentanamine	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}-N- methylpiperidine-4-carboxamide	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-[(1-{4-[(3S)-2,3- dihydro[1,4]dioxino[2,3- b]pyridin-3-yl]benzyl}piperidin-3- yl)methyl]pyrrolidin-2-one	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
N-{4-[(2S)-2,3-dihydro-1,4- benzodioxin-2-yl]benzyl}-N- ethylcyclopentanamine	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(1S,5R)-3-[[4-[(3S)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl]phenyl]methyl]-N-[(2S)-2-hydroxypropyl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
(1S,5R)-3-[[4-[(3S)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl]phenyl]methyl]-N-[(2S)-1-hydroxypropan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-piperidine-4-carboxylic acid (2-hydroxy-2-methyl-propyl)- amide	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy
1-{(1S,4S)-5-[(S)-4-(2,3-Dihydro- [1,4]dioxino[2,3-b]pyridin-3-yl)- benzyl]-2,5-diaza- bicyclo[2.2.2]oct-2-yl}-2- hydroxy-ethanone	IC50	0.17 nM	US-9662339: Benzodioxane inhibitors of leukotriene production for combination therapy

ChEMBL bioactivities

1345 potent at pChembl≥5 of 1423 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.38	IC50	0.042	nM	CHEMBL5924242
10.15	IC50	0.07	nM	CHEMBL6060058
10.10	IC50	0.08	nM	CHEMBL5797467
10.05	IC50	0.09	nM	CHEMBL6015103
10.05	IC50	0.09	nM	CHEMBL5990393
10.05	IC50	0.09	nM	CHEMBL5780202
10.05	IC50	0.09	nM	CHEMBL5904849
10.00	IC50	0.1	nM	CHEMBL5836580
10.00	IC50	0.1	nM	CHEMBL5809166
10.00	IC50	0.1	nM	CHEMBL5970714
10.00	IC50	0.1	nM	CHEMBL5862086
9.96	IC50	0.11	nM	CHEMBL5908013
9.96	IC50	0.11	nM	CHEMBL6046439
9.92	IC50	0.12	nM	CHEMBL4852381
9.92	IC50	0.12	nM	CHEMBL5840601
9.92	IC50	0.12	nM	CHEMBL5822057
9.92	IC50	0.12	nM	CHEMBL6064488
9.89	IC50	0.13	nM	CHEMBL5956548
9.89	IC50	0.13	nM	CHEMBL5880832
9.89	IC50	0.13	nM	CHEMBL5839428
9.89	IC50	0.13	nM	CHEMBL5785797
9.89	IC50	0.13	nM	CHEMBL6036521
9.85	IC50	0.14	nM	CHEMBL6015459
9.85	IC50	0.14	nM	CHEMBL6009509
9.85	IC50	0.14	nM	CHEMBL5754908
9.85	IC50	0.14	nM	CHEMBL5971194
9.85	IC50	0.14	nM	CHEMBL5854837
9.82	IC50	0.15	nM	CHEMBL5785372
9.82	IC50	0.15	nM	CHEMBL5895730
9.82	IC50	0.15	nM	CHEMBL5791547
9.82	IC50	0.15	nM	CHEMBL5882143
9.82	IC50	0.15	nM	CHEMBL6006360
9.80	IC50	0.16	nM	CHEMBL5774953
9.80	IC50	0.16	nM	CHEMBL5918365
9.80	IC50	0.16	nM	CHEMBL5832817
9.80	IC50	0.16	nM	CHEMBL5917850
9.80	IC50	0.16	nM	CHEMBL5878596
9.80	IC50	0.16	nM	CHEMBL5958377
9.80	IC50	0.16	nM	CHEMBL6045833
9.80	IC50	0.16	nM	CHEMBL5880083
9.80	IC50	0.16	nM	CHEMBL5888738
9.80	IC50	0.16	nM	CHEMBL5945629
9.80	IC50	0.16	nM	CHEMBL5978426
9.77	IC50	0.17	nM	CHEMBL5765160
9.77	IC50	0.17	nM	CHEMBL6019068
9.77	IC50	0.17	nM	CHEMBL5923789
9.77	IC50	0.17	nM	CHEMBL5968539
9.77	IC50	0.17	nM	CHEMBL5806002
9.77	IC50	0.17	nM	CHEMBL5973813
9.77	IC50	0.17	nM	CHEMBL5963279

PubChem BioAssay actives

952 with measured affinity, of 1561 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
(3S)-3-amino-4-[5-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]tetrazol-2-yl]butanoic acid	1775199: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration <1 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0001	uM
N-[8-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]-8-azabicyclo[3.2.1]octan-3-yl]acetamide	718575: Inhibition of human recombinant LTA4 hydrolase expressed in SF9 cells using LTA4 as substrate assessed as LTB4 production incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0003	uM
3-[methyl-[3-[4-(4-phenylphenoxy)phenoxy]propyl]amino]propanoic acid	594263: Inhibition of human leukotriene A4 hydrolase	ic50	0.0005	uM
1-[2-(4-benzylphenoxy)ethyl]imidazo[4,5-b]pyridine-5-carbonitrile	99748: In vitro inhibition of recombinant human leukotriene A4 hydrolase.	ic50	0.0008	uM
4-[2-[(1R,5S)-3-[4-[4-(1,3-oxazol-2-yl)phenoxy]anilino]-8-azabicyclo[3.2.1]octan-8-yl]ethyl]benzoic acid	340435: Inhibition of LTA4 hydrolase	ic50	0.0010	uM
(2S)-2-[[4-(4-thiophen-3-ylphenoxy)phenoxy]methyl]piperidine	480991: Inhibition of human LTA4H hydrolysis assessed as inhibition of Ca2+ ionophore-stimulated LTB4 formation in human whole blood by ELISA	ic50	0.0010	uM
N-[8-[[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]methyl]-8-azabicyclo[3.2.1]octan-3-yl]acetamide	718575: Inhibition of human recombinant LTA4 hydrolase expressed in SF9 cells using LTA4 as substrate assessed as LTB4 production incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0010	uM
N-(benzenesulfonyl)-3-[3-(4-benzylphenoxy)propyl-methylamino]propanamide	99745: Inhibition of human leukotriene A4 hydrolase (LTA-4).	ic50	0.0010	uM
2-[4-(4-benzylphenoxy)butylamino]acetic acid	99745: Inhibition of human leukotriene A4 hydrolase (LTA-4).	ic50	0.0013	uM
3-[3-(4-benzylphenoxy)propyl-methylamino]-N-methylsulfonylpropanamide	99745: Inhibition of human leukotriene A4 hydrolase (LTA-4).	ic50	0.0013	uM
1-(4-phenoxyphenyl)piperazine	445449: Inhibition of human recombinant LTA4H hydrolysis assessed as inhibition of LTB4 formation by LC-MS/MS	ic50	0.0014	uM
6-[[(2S)-2-amino-3-(4-phenylmethoxyphenyl)propyl]-hydroxyamino]-6-oxohexanoic acid	382285: Inhibition of human recombinant LTA4-h by peptidase assay	ki	0.0016	uM
N-[(1S,5R)-8-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-8-azabicyclo[3.2.1]octan-3-yl]acetamide	724278: Inhibition of recombinant human LTA4H expressed in Sf9 cells using LTA4 as substrate incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0016	uM
N-[(1R,5S)-8-[[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]methyl]-8-azabicyclo[3.2.1]octan-3-yl]acetamide	1775199: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration <1 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0019	uM
4-[2-[3-[4-[4-(1,3-oxazol-2-yl)phenoxy]anilino]piperidin-1-yl]ethyl]benzoic acid	340435: Inhibition of LTA4 hydrolase	ic50	0.0020	uM
3-[methyl-[3-[4-(thiophen-3-ylmethyl)phenoxy]propyl]amino]propanoic acid	594263: Inhibition of human leukotriene A4 hydrolase	ic50	0.0020	uM
3-[3-(4-benzylphenoxy)propyl-methylamino]propanoic acid;hydrochloride	99745: Inhibition of human leukotriene A4 hydrolase (LTA-4).	ic50	0.0025	uM
3-[3-(4-benzylphenoxy)propyl-methylamino]propanoic acid	99749: Inhibition of leukotriene A4 hydrolase in human recombinant assay	ic50	0.0025	uM
(3R)-3-amino-4-[5-[4-(1,3-benzothiazol-2-yloxy)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3R)-3-amino-4-[5-[4-[(5-chloro-2-pyridinyl)oxy]phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3R)-3-amino-4-[5-[4-(4-chlorophenoxy)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3R)-3-amino-4-[5-[4-(2-phenylethoxy)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3R)-3-amino-4-[5-[4-(4-fluorophenoxy)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3S)-3-amino-4-[5-[4-(1,3-benzothiazol-2-yloxy)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3S)-3-amino-4-[5-[4-[(2R)-1-phenylpropan-2-yl]oxyphenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3S)-3-amino-4-[5-[4-(phenylmethoxymethyl)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(2S)-2-amino-3-[3-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]pyrazol-1-yl]propan-1-ol	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(2S)-2-amino-3-[3-[4-[[5-(1H-pyrazol-5-yl)-2-pyridinyl]oxy]phenyl]-1,2,4-oxadiazol-5-yl]propan-1-ol	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(2S)-2-amino-3-[5-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]tetrazol-2-yl]propan-1-ol	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(2S)-2-amino-3-[3-[4-[[3-fluoro-5-(1H-pyrazol-5-yl)-2-pyridinyl]oxy]phenyl]pyrazol-1-yl]propan-1-ol	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(2R)-2-amino-3-[5-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]tetrazol-2-yl]propan-1-ol	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
2-[5-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]tetrazol-2-yl]ethanamine	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
4-[[(2R,5R)-2,5-dimethyl-4-[[4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]methyl]piperazin-1-yl]methyl]benzoic acid	2081540: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 30 mins by fluorescence based analysis	ic50	0.0030	uM
N,N-dimethyl-1-[5-[[5-(1H-pyrazol-5-yl)-2-pyridinyl]oxy]-2-pyridinyl]methanamine	2081540: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 30 mins by fluorescence based analysis	ic50	0.0030	uM
2-(piperidin-1-ylmethyl)-5-[[5-(1H-pyrazol-5-yl)-2-pyridinyl]oxy]pyridine	2081540: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 30 mins by fluorescence based analysis	ic50	0.0030	uM
1-[2-[[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]methyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]ethanone	718575: Inhibition of human recombinant LTA4 hydrolase expressed in SF9 cells using LTA4 as substrate assessed as LTB4 production incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0030	uM
2-[4-(piperidin-1-ylmethyl)phenoxy]-[1,3]thiazolo[4,5-b]pyridine	718575: Inhibition of human recombinant LTA4 hydrolase expressed in SF9 cells using LTA4 as substrate assessed as LTB4 production incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0030	uM
4-[2-[methyl-[3-[methyl-[2-oxo-2-(4-phenoxyanilino)ethyl]amino]propyl]amino]ethyl]benzoic acid	340108: Inhibition of LTA4 hydrolase by hydrolase assay	ic50	0.0030	uM
4-[[(1R,5S)-3-(4-benzylanilino)-8-azabicyclo[3.2.1]octan-8-yl]methyl]benzoic acid	340435: Inhibition of LTA4 hydrolase	ic50	0.0030	uM
4-[[3-[[2-(4-benzylanilino)-2-oxoethyl]-methylamino]propyl-methylamino]methyl]benzoic acid	340108: Inhibition of LTA4 hydrolase by hydrolase assay	ic50	0.0030	uM
4-[[methyl-[3-[4-[4-(1,3-oxazol-2-yl)phenoxy]anilino]propyl]amino]methyl]benzoic acid	340435: Inhibition of LTA4 hydrolase	ic50	0.0030	uM
4-[2-[4-[4-[4-(1,3-oxazol-2-yl)phenoxy]anilino]piperidin-1-yl]ethyl]benzoic acid	340435: Inhibition of LTA4 hydrolase	ic50	0.0030	uM
2-[4-(2-piperidin-1-ylethyl)phenoxy]-[1,3]thiazolo[4,5-b]pyridine	718575: Inhibition of human recombinant LTA4 hydrolase expressed in SF9 cells using LTA4 as substrate assessed as LTB4 production incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0030	uM
1-[1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl]pyrrolidin-2-one	724278: Inhibition of recombinant human LTA4H expressed in Sf9 cells using LTA4 as substrate incubated for 10 mins prior to substrate addition measured after 10 to 30 mins by enzyme immunoassay	ic50	0.0030	uM
4-[[(1S,4S)-5-[[4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]benzoic acid	2023345: Inhibition of LTA4H (unknown origin)	ic50	0.0030	uM
(3S)-3-amino-4-[5-[4-(4-chlorophenoxy)phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0030	uM
(3R)-3-amino-4-[5-[4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0031	uM
(3R)-3-amino-4-[5-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]tetrazol-2-yl]butanoic acid	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0035	uM
2-[5-[4-(4-methylphenoxy)phenyl]tetrazol-2-yl]ethanamine	1775159: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay	ic50	0.0036	uM
(2S)-2-amino-3-[3-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenyl]-1,2,4-oxadiazol-5-yl]propan-1-ol	2023347: Inhibition of LTA4H (unknown origin) using Arg-AMC as substrate preincubated with compound for 15 mins followed by substrate addition and measured after every 10 mins for 300 mins by fluorescence based assay	ic50	0.0036	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Leukotriene B4	decreases reaction, increases chemical synthesis	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
trichostatin A	affects expression	1
tetrahydropalmatine	decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
cupric chloride	decreases expression	1
propanethiol	decreases reaction, increases chemical synthesis, increases hydrolysis	1
2-chloroethyl ethyl sulfide	increases expression	1
quinoline	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
cyclohexene	increases chemical synthesis, increases hydrolysis, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
montelukast	affects response to substance	1
chloropicrin	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1

ChEMBL screening assays

159 unique, capped per target: 154 binding, 3 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005602	Binding	Inhibition of human recombinant leukotriene A4 hydrolase	Synthesis and biological evaluation of N-mercaptoacylproline and N-mercaptoacylthiazolidine-4-carboxylic acid derivatives as leukotriene A4 hydrolase inhibitors. — Bioorg Med Chem Lett
CHEMBL4009226	ADMET	Inhibition of recombinant human LTA4H aminopeptidase activity expressed in Escherichia coli BL21 (DE3) pLysS assessed as formation of p-NA from Ala-p-NA preincubated for 10 mins followed by substrate addition measured after 10 mins	Drug Repurposing of Histone Deacetylase Inhibitors That Alleviate Neutrophilic Inflammation in Acute Lung Injury and Idiopathic Pulmonary Fibrosis via Inhibiting Leukotriene A4 Hydrolase and Blocking LTB4 Biosynthesis. — J Med Chem
CHEMBL701917	Functional	Inhibition of human whole blood LTB-4 production (Leukotriene B-4).	Synthesis of potent leukotriene A(4) hydrolase inhibitors. Identification of 3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3AC	Abcam HEK293T LTA4H KO	Transformed cell line	Female

Clinical trials (associated diseases)

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