EPHX2

Summary

EPHX2 (epoxide hydrolase 2, HGNC:3402) is a protein-coding gene on chromosome 8p21.2-p21.1, encoding Bifunctional epoxide hydrolase 2 (P34913). Bifunctional enzyme.

This gene encodes a member of the epoxide hydrolase family. The protein, found in both the cytosol and peroxisomes, binds to specific epoxides and converts them to the corresponding dihydrodiols. Mutations in this gene have been associated with familial hypercholesterolemia. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 2053 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholesterolemia, familial, 1 (No Known Disease Relationship, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 148 total
• Phenotypes (HPO): 7
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001979

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3402
Approved symbol	EPHX2
Name	epoxide hydrolase 2
Location	8p21.2-p21.1
Locus type	gene with protein product
Status	Approved
Aliases	ABHD20, sEH
Ensembl gene	ENSG00000120915
Ensembl biotype	protein_coding
OMIM	132811
Entrez	2053

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000380476, ENST00000517536, ENST00000518328, ENST00000518379, ENST00000520623, ENST00000520666, ENST00000521400, ENST00000521684, ENST00000521780, ENST00000521924, ENST00000523326, ENST00000523827, ENST00000850871, ENST00000872955, ENST00000872956, ENST00000872957, ENST00000872958, ENST00000872959, ENST00000872960, ENST00000872961, ENST00000872962, ENST00000953798, ENST00000953799, ENST00000953800

RefSeq mRNA: 12 — MANE Select: NM_001979 NM_001256482, NM_001256483, NM_001256484, NM_001414016, NM_001414017, NM_001414018, NM_001414019, NM_001414020, NM_001414021, NM_001414022, NM_001414023, NM_001979

CCDS: CCDS59097, CCDS59098, CCDS6060

Canonical transcript exons

ENST00000521400 — 19 exons

Exon	Start	End
ENSE00000818632	27544186	27544244
ENSE00000818633	27543749	27543829
ENSE00000818634	27541473	27541542
ENSE00000818635	27540554	27540656
ENSE00001041934	27538659	27538692
ENSE00002094571	27544444	27545564
ENSE00003473677	27536784	27536855
ENSE00003478477	27518038	27518072
ENSE00003503426	27503604	27503763
ENSE00003516483	27500926	27501010
ENSE00003522589	27515718	27515813
ENSE00003527034	27520883	27520909
ENSE00003565838	27522423	27522508
ENSE00003571420	27516320	27516398
ENSE00003571799	27525362	27525473
ENSE00003625617	27506872	27506994
ENSE00003647949	27504956	27505146
ENSE00003688118	27511836	27511910
ENSE00004282578	27491143	27491309

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3365 / max 373.0203, expressed in 1208 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88152	13.2081	1206
88151	0.1285	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.51	gold quality
mucosa of transverse colon	UBERON:0004991	97.22	gold quality
right adrenal gland	UBERON:0001233	96.91	gold quality
right adrenal gland cortex	UBERON:0035827	96.82	gold quality
rectum	UBERON:0001052	96.68	gold quality
left adrenal gland cortex	UBERON:0035825	96.20	gold quality
left adrenal gland	UBERON:0001234	96.12	gold quality
body of pancreas	UBERON:0001150	95.98	gold quality
adult mammalian kidney	UBERON:0000082	95.74	gold quality
right uterine tube	UBERON:0001302	95.73	gold quality
liver	UBERON:0002107	95.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.44	gold quality
transverse colon	UBERON:0001157	95.01	gold quality
adrenal gland	UBERON:0002369	94.76	gold quality
jejunal mucosa	UBERON:0000399	94.72	gold quality
small intestine	UBERON:0002108	94.63	gold quality
adrenal tissue	UBERON:0018303	94.61	gold quality
adenohypophysis	UBERON:0002196	94.47	gold quality
adrenal cortex	UBERON:0001235	94.43	gold quality
apex of heart	UBERON:0002098	94.37	gold quality
skin of abdomen	UBERON:0001416	93.78	gold quality
left ovary	UBERON:0002119	93.75	gold quality
duodenum	UBERON:0002114	93.55	gold quality
lower esophagus mucosa	UBERON:0035834	93.28	gold quality
skin of leg	UBERON:0001511	93.14	gold quality
pituitary gland	UBERON:0000007	93.08	gold quality
pancreas	UBERON:0001264	92.78	gold quality
right ovary	UBERON:0002118	92.74	gold quality
prostate gland	UBERON:0002367	92.33	gold quality
intestine	UBERON:0000160	92.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HMGCR	Activation

Upstream regulators (CollecTRI, top): AP1, FOS, HNF4A, JUN, SP1

miRNA regulators (miRDB)

24 targeting EPHX2, 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-589-3P	99.91	69.62	2088
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-5579-3P	97.00	68.81	1111

Literature-anchored findings (GeneRIF, showing 40)

• Common polymorphisms within EPHX2 do not appear to be important risk factors for Parkinson’s disease. (PMID:11692079)
• Close association of soluble epoxide hydrolase gene G860A (Arg287Gln) polymorphism with insulin resistance in type 2 diabetic patients. (PMID:15845398)
• Multiple variants exist within or near the EPHX2 gene, with greatly contrasting relationships to ischemic stroke incidence; some associated with a higher incidence and others with a lower incidence. (PMID:16115816)
• Soluble epoxide epoxygenase-related SNP is not associated with increased risk of hypertension in the African American population. (PMID:16202848)
• Consistent with the finding of isoprenoid phosphates as substrates for sEH, we identified isoprenoid-derived N-terminal inhibitors with IC50 values ranging from 0.84 (+/-0.9) to 55.1 (+/-30.7) microM. (PMID:16414022)
• EPHX2 has an emerging role as a risk factor for atherosclerosis, whose effects are influenced by smoking (PMID:16545818)
• EPHX2 as a potential cardiovascular disease-susceptibility gene. (PMID:16595607)
• comprehensive analysis of the distribution of sEH, CYP2C8, 2C9 and 2J2 in human neoplastic tissues using tissue micro-arrays (PMID:16957870)
• human EPHX2 mutations may in part explain the genetic variability in sensitivity to ischemic brain injury and stroke outcome (PMID:17460077)
• AP-1 activation is involved in the transcriptional up-regulation of sEH by angiotensin II (Ang II) in endothelial cells, which may contribute to Ang II-induced hypertension (PMID:17495027)
• Our results demonstrated significant association with exon 3 variant genotypes of the mEH alone or in combination with tobacco users (p < 0.005), whereas in exon 4 genotypes, no association was observed. (PMID:17919073)
• The minimal promoter was identified as a GC-rich region between nts -374 and +28 with respect to the putative transcriptional start site. (PMID:18078836)
• Our results indicate differential localization of sEH in the human brain, thus suggestive of an essential role for this enzyme in the central nervous system. (PMID:18319271)
• Three EPHX2 single nucleotide polymorphisms showed associations with an increased risk for ischemic stroke (PMID:18323494)
• Results provide additional evidence that EPHX2 contributes to the risk of subclinical cardiovascular disease. (PMID:18537101)
• Presence of a variant allele in EPHXw is associated with a protective role for kidney allograft function. (PMID:18589104)
• Results describe the catalytic mechanism of dephosphorylation by soluble epoxide hydrolase, using phosphatase active-site mutants created by site-directed mutagenesis. (PMID:18775727)
• Data indicate that the activity of soluble epoxide hydrolase can be regulated by the tyrosine nitration of the protein. (PMID:19704161)
• EPHX2 K55R polymorphism is not associated with restenosis after PCI, with incidence of coronary heart disease, or with an increased risk of hypertension. (PMID:19814804)
• Results show that no relationship exists between EPHX2 and risk of ischemic stroke, myocardial infarction, and ischemic heart disease. (PMID:19940276)
• The functional K55R polymorphism of the EPHX2 gene confers a higher risk of hypertension prevalence and increases the risk of incident ischemic stroke in male homozygotes. (PMID:20065888)
• SP-1 is involved in the decrease in the transcription of sEH as a result of DNA methylation in HepG2 cells, which might contribute to epigenetic mechanism-induced carcinogenesis in hepatocytes. (PMID:20888937)
• Genetic variation in epoxide hydrolase 2 is associated with forearm vasodilator responses in a bradykinin receptor- and endothelium-independent manner, suggesting an important role for soluble epoxide hydrolase in regulating vascular function in humans. (PMID:21098312)
• The PLA2G7, HPGD, EPHX2, and CYP4F8 genes are highly expressed in prostate cancer. (PMID:21281786)
• In patients with IgA nephropathy, some single nucleotide polymorphisms of EPHX2 were associated with more rapid disease progression. (PMID:21429967)
• This case-control study as well as meta-analysis suggested no association between CYP2J2 G-50T and EPHX2 R287Q and the risk of developing coronary artery disease . (PMID:21642892)
• sEH is one of the etiological factors of cardiovascular diseases, and plays an important role in the progression of myocardium ischemia. (PMID:21704394)
• The essential hypertension in Kazaks in Xinjiang is not associated with rs751141G/A gene polymorphism, but is associated with rs751141G/A allele gene polymorphism of EPHX2. (PMID:22336502)
• ATF6 activation and DNA demethylation may coordinately contribute to Hcy-induced sEH expression and endothelial activation. (PMID:22354938)
• These findings also underline possible cellular mechanisms by which both activities of sEH (EH and phosphatase) may have complementary or opposite roles. (PMID:22387545)
• investigation of role of cytoplasmic Ephx2 in diabetic nephropathy by gene disruption techniques: Ephx2 gene inhibition (or added epoxyeicosatrienoic acids) protects renal proximal tubular cell line from tumor necrosis factor-alpha-induced apoptosis. (PMID:22739108)
• Study analyzed the association between four SNPs in the EPHX1 and EPHX2 and the risk of oligozoospermia and asthenospermia; rs1051740, rs2234922 and rs751141 were not associated with oligozoospermia and asthenospermia and rs1042064 was a protective factor in idiopathic male infertility. (PMID:22986331)
• Evidence suggests that modulation of plasma levels of epoxyeicosatrienoic acid (EET) (for example, down-regulation of EET in patients with renovascular disease-associated hypertension) is due, in part, to up-regulation of EPHX2. [REVIEW] (PMID:23011468)
• Upregulation of sEH in proximal tubular cells in chronic proteinuric kidney diseases may mediate proteinuria-induced renal damage. (PMID:23152298)
• the importance of sEH in MCP-1-regulated monocyte chemotaxis (PMID:23160182)
• Soluble epoxide hydrolase dimerization is required for hydrolase activity (PMID:23362272)
• sEH is a physiological modulator of ER stress and a potential target for mitigating complications associated with obesity (PMID:23576437)
• Presence of single nucleotide polymorphism rs751141 of EPHX2 is associated with significantly increased risk of atrial fibrillation recurrence following catheter ablation. (PMID:23711456)
• Findings suggest a novel association of gene variants within EPHX2 to susceptibility to anorexia nervosa and provide a foundation for future study of this important yet poorly understood condition (PMID:23999524)
• The WT sEH formed a very tight dimer, with a KD/M in the low picomolar range. Only R287Q resulted in a large change of the KD/M However, human tissue concentrations of sEH suggest that it is always in its dimer form independently of the SNP. (PMID:24771868)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	ephx2	ENSDARG00000040255
mus_musculus	Ephx2	ENSMUSG00000022040
rattus_norvegicus	Ephx2	ENSRNOG00000017286
drosophila_melanogaster	CG5704	FBGN0026570
drosophila_melanogaster	CG5707	FBGN0026593
drosophila_melanogaster	CG15879	FBGN0035309
drosophila_melanogaster	CG15820	FBGN0035312
drosophila_melanogaster	CG11309	FBGN0037070
drosophila_melanogaster	CG7632	FBGN0037071
caenorhabditis_elegans	C31H5.1	WBGENE00007854
caenorhabditis_elegans		WBGENE00017335
caenorhabditis_elegans		WBGENE00018077
caenorhabditis_elegans		WBGENE00019525
caenorhabditis_elegans		WBGENE00022258
caenorhabditis_elegans		WBGENE00022259
caenorhabditis_elegans		WBGENE00022260

Paralogs (12): ABHD5 (ENSG00000011198), ABHD4 (ENSG00000100439), EPHX3 (ENSG00000105131), ABHD11 (ENSG00000106077), MEST (ENSG00000106484), ABHD14B (ENSG00000114779), ABHD8 (ENSG00000127220), BPHL (ENSG00000137274), ABHD6 (ENSG00000163686), EPHX4 (ENSG00000172031), SERHL2 (ENSG00000183569), ABHD14A (ENSG00000248487)

Protein

Protein identifiers

Bifunctional epoxide hydrolase 2 — P34913 (reviewed: P34913)

All UniProt accessions (5): E5RFH6, E5RFU2, E5RI53, P34913, H0YAW7

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. Bifunctional enzyme. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic acid. Has phosphatase activity toward lyso-glycerophospholipids with also some lower activity toward lysolipids of sphingolipid and isoprenoid phosphates.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Peroxisome.

Post-translational modifications. The N-terminus is blocked. The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.

Activity regulation. Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[’]-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA). Phosphatase activity is inhibited by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic acids and fatty acids such as palmitic acid and lauric acid.

Domain organisation. The N-terminal domain has phosphatase activity. The C-terminal domain has epoxide hydrolase activity.

Induction. By compounds that cause peroxisome proliferation such as clofibrate, tiadenol and fenofibrate.

Similarity. Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P34913-1	1	yes
P34913-2	2
P34913-3	3

RefSeq proteins (12): NP_001243411, NP_001243412, NP_001243413, NP_001400945, NP_001400946, NP_001400947, NP_001400948, NP_001400949, NP_001400950, NP_001400951, NP_001400952, NP_001970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR000639	Epox_hydrolase-like	Family
IPR006439	HAD-SF_hydro_IA	Family
IPR011945	HAD-SF_ppase_IA/epoxid_hydro_N	Domain
IPR023198	PGP-like_dom2	Homologous_superfamily
IPR023214	HAD_sf	Homologous_superfamily
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF00561, PF00702

Enzyme classification (BRENDA):

• EC 3.1.3.106 — 2-lysophosphatidate phosphatase (BRENDA: 7 organisms, 32 substrates, 22 inhibitors, 13 Km, 4 kcat entries)
• EC 3.3.2.10 — soluble epoxide hydrolase (BRENDA: 48 organisms, 343 substrates, 1613 inhibitors, 109 Km, 60 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
TRANS-STILBENE OXIDE	0.0017–0.011	12
14,15-EPOXYEICOSATRIENOIC ACID	0.007–0.076	7
TRANS-1,3-DIPHENYLPROPENE OXIDE	0.0033–0.0253	6
(R)-STYRENE OXIDE	0.001–21.8	5
(S)-STYRENE OXIDE	0.07–8.33	5
1-MYRISTOYL-SN-GLYCEROL 3-PHOSPHATE	0.006–0.019	5
2,3-EPOXY-1,3-DIPHENYL-PROPANE	0.0043–0.0083	5
ATTOPHOS	0.0074–0.017	5
EPOXY FLUOR 7	0.0058–0.0151	5
CIS-STILBENE OXIDE	0.027–0.076	4
STYRENE OXIDE	1.36–3.4	3
TRANS-DIPHENYLPROPENE OXIDE	0.0078–0.01	3
1-ARACHIDONOYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.0059–0.013	2
1-OLEOYL-2-LYSO-SN-GLYCEROL 3-PHOSPHATE	0.0062–0.0069	2
(10R)-HYDROXY-(11S,12S)-EPOXY-(5Z,8Z,14Z)-EICOSA	0.0108–0.0147	2

Catalyzed reactions (Rhea), 12 shown:

• (9S,10S)-10-hydroxy-9-(phosphooxy)octadecanoate + H2O = (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate (RHEA:16537)
• an epoxide + H2O = an ethanediol (RHEA:19037)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphate (RHEA:39835)
• 9,10-epoxy-(12Z)-octadecenoate + H2O = 9,10-dihydroxy-(12Z)-octadecenoate (RHEA:44032)
• 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = 14,15-dihydroxy-(5Z,8Z,11Z)-eicosatrienoate (RHEA:44040)
• 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = 11,12-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate (RHEA:44044)
• 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = 8,9-dihydroxy-(5Z,11Z,14Z)-eicosatrienoate (RHEA:44048)
• 12-phosphooxy-(9Z)-octadecenoate + H2O = 12-hydroxy-(9Z)-octadecenoate + phosphate (RHEA:45272)
• 12-phosphooxy-(9E)-octadecenoate + H2O = 12-hydroxy-(9E)-octadecenoate + phosphate (RHEA:45276)
• 12-(phosphooxy)octadecanoate + H2O = 12-hydroxyoctadecanoate + phosphate (RHEA:45280)
• 8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate + H2O = (8,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoate (RHEA:50896)
• 10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate + H2O = (10,11S,12R)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoate (RHEA:50900)

UniProt features (103 total): helix 34, strand 19, sequence variant 10, turn 9, modified residue 8, binding site 5, sequence conflict 5, active site 3, region of interest 2, splice variant 2, mutagenesis site 2, chain 1, domain 1, lipid moiety-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

139 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8QZD	X-RAY DIFFRACTION	1.3
8S77	X-RAY DIFFRACTION	1.36
8S75	X-RAY DIFFRACTION	1.42
8QMZ	X-RAY DIFFRACTION	1.47
8S76	X-RAY DIFFRACTION	1.48
8QN0	X-RAY DIFFRACTION	1.49
5MWA	X-RAY DIFFRACTION	1.55
9EXM	X-RAY DIFFRACTION	1.64
5AM2	X-RAY DIFFRACTION	1.7
5AI0	X-RAY DIFFRACTION	1.75
5AK4	X-RAY DIFFRACTION	1.79
4X6X	X-RAY DIFFRACTION	1.8
5AI9	X-RAY DIFFRACTION	1.8
5ALV	X-RAY DIFFRACTION	1.8
5AKI	X-RAY DIFFRACTION	1.81
5AI8	X-RAY DIFFRACTION	1.85
5ALI	X-RAY DIFFRACTION	1.85
9QZR	X-RAY DIFFRACTION	1.85
5ALU	X-RAY DIFFRACTION	1.87
5AM4	X-RAY DIFFRACTION	1.87
5AM0	X-RAY DIFFRACTION	1.88
5AIC	X-RAY DIFFRACTION	1.89
5AKK	X-RAY DIFFRACTION	1.9
5ALH	X-RAY DIFFRACTION	1.9
5ALY	X-RAY DIFFRACTION	1.9
5AI4	X-RAY DIFFRACTION	1.93
9QZA	X-RAY DIFFRACTION	1.93
3I28	X-RAY DIFFRACTION	1.95
5AIB	X-RAY DIFFRACTION	1.95
5ALE	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34913-F1	93.54	0.81

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 (3): 335 (nucleophile); 466 (proton donor); 524 (proton acceptor)

Ligand- & substrate-binding residues (5): 123–124; 185; 383; 9; 11

Post-translational modifications (9): 43, 55, 191, 215, 370, 421, 455, 554, 522

Mutagenesis-validated functional residues (2):

Position	Phenotype
9	loss of phosphatase activity.
522	loss of s-(15-deoxy-delta12,14-prostaglandin j2-9-yl)cysteine-induced inhibition of epoxide hydrolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2142670	Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)
R-HSA-9018682	Biosynthesis of maresins
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 269 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_LIPID_MODIFICATION, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_STEROL_HOMEOSTASIS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_GROWTH, GOBP_LIPID_HOMEOSTASIS, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, MODULE_75, chr8p21, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (10): regulation of cell growth (GO:0001558), response to toxic substance (GO:0009636), positive regulation of gene expression (GO:0010628), dephosphorylation (GO:0016311), cholesterol homeostasis (GO:0042632), stilbene catabolic process (GO:0046272), phospholipid dephosphorylation (GO:0046839), regulation of cholesterol metabolic process (GO:0090181), epoxide metabolic process (GO:0097176), lipid metabolic process (GO:0006629)

GO Molecular Function (11): magnesium ion binding (GO:0000287), epoxide hydrolase activity (GO:0004301), toxic substance binding (GO:0015643), phosphatase activity (GO:0016791), 10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity (GO:0033885), lipid phosphatase activity (GO:0042577), protein homodimerization activity (GO:0042803), lysophosphatidic acid phosphatase activity (GO:0052642), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Arachidonate metabolism	1
Biosynthesis of DHA-derived SPMs	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatase activity	3
cellular anatomical structure	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
response to chemical	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
phosphate-containing compound metabolic process	1
sterol homeostasis	1
benzene-containing compound metabolic process	1
olefinic compound catabolic process	1
dephosphorylation	1
lipid modification	1
cholesterol metabolic process	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1
metabolic process	1
primary metabolic process	1
metal ion binding	1
ether hydrolase activity	1
binding	1
phosphoric ester hydrolase activity	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
catalytic activity	1
cation binding	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHX2	PLPP6	Q8IY26	808
EPHX2	SETBP1	Q9Y6X0	790
EPHX2	CYP2J2	P51589	786
EPHX2	FUT2	Q10981	775
EPHX2	PLPPR4	Q7Z2D5	739
EPHX2	PLPP1	O14494	728
EPHX2	PPIG	Q13427	721
EPHX2	CYP2C8	P10632	700
EPHX2	EPHX1	P07099	690
EPHX2	CYP2C18	P33260	685
EPHX2	CYP2C9	P11712	645
EPHX2	MGLL	Q99685	637
EPHX2	EPHA4	P54764	637
EPHX2	PLPP3	O14495	625
EPHX2	PLA2G4A	P47712	621

IntAct

8 interactions, top by confidence:

A	B	Type	Score
EPHX2	MVP	psi-mi:“MI:0915”(physical association)	0.370
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
CAT	VWA8	psi-mi:“MI:2364”(proximity)	0.270
TERF1	EPHX2	psi-mi:“MI:0915”(physical association)	0.000
EPHX2		psi-mi:“MI:0915”(physical association)	0.000
NIPSNAP3A	EPHX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): HDHD1 (Co-fractionation), EPHX2 (Proximity Label-MS), EPHX2 (Protein-RNA), EPHX2 (Co-fractionation), ACAA2 (Co-fractionation), BCAT1 (Co-fractionation), NPEPPS (Co-fractionation), EPHX2 (Co-fractionation), EPHX2 (Co-fractionation), EPHX2 (Co-fractionation), EPHX2 (Co-fractionation), EPHX2 (Co-fractionation), FKBP4 (Co-fractionation), EPHX2 (Affinity Capture-MS), EPHX2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A068ACU9, A0A0S6XGG4, A0A0S6XGG5, A0A0U5GNT1, A0A1B4XBH6, A0A1B4XBK1, A0A1B5L8S2, A0A1C8AX29, A0A1L9WUM2, A0A1W5T1Y7, A0A346RP51, A0A411KUP9, A0A481WQ01, A0A4P8W7Y2, A0A6J4B4M6, A0A7L8UVC6, A0A7L9F0X4, A0A8F4NU75, A0A8F4NUL3, A1CLZ0, A8AKP9, B7LNG1, G4MVZ4, H1AE12, O02734, O95822, P12617, P34913, P34914, P80299, P9WEU7, P9WEZ7, Q00706, Q0JJD4, Q0V6Q1, Q2KIE6, Q4WAZ8, Q4WD45, Q4WZB3, Q5AV07

Diamond homologs: A0A0U5GNT1, A0A6A6H2E0, P34913, P34914, P80299, P9WEM0, Q2UEK4, Q2UEL0, Q58832, A0A1L5BTC1, A0A242M8J4, A1KLS7, A4JPX5, A5U5S9, A7YY28, A9W3H8, B0SW62, B0SY51, B2HJU9, B2JQW2, B4RF90, B7KWT4, B8H1Q3, C1AF48, C7TMK0, D4Z2G1, I6YC03, I6YGS0, O05235, O05691, O31158, O31168, O32234, P0A3G2, P0A3G3, P0A3G4, P0DO68, P0DO69, P0DO70, P19076

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3028 predictions. Top by Δscore:

Variant	Effect	Δscore
8:27490857:C:G	donor_gain	1.0000
8:27491306:CCAGG:C	donor_loss	1.0000
8:27491308:AGGT:A	donor_loss	1.0000
8:27491310:G:GA	donor_loss	1.0000
8:27491311:T:A	donor_loss	1.0000
8:27503602:AGT:A	acceptor_gain	1.0000
8:27503602:AGTG:A	acceptor_gain	1.0000
8:27503603:G:GC	acceptor_gain	1.0000
8:27503603:GT:G	acceptor_gain	1.0000
8:27503603:GTG:G	acceptor_gain	1.0000
8:27503603:GTGG:G	acceptor_gain	1.0000
8:27503603:GTGGA:G	acceptor_gain	1.0000
8:27503759:GAAAG:G	donor_gain	1.0000
8:27503761:AAGGT:A	donor_loss	1.0000
8:27503762:AGGTA:A	donor_loss	1.0000
8:27503763:GGT:G	donor_loss	1.0000
8:27503764:G:GG	donor_gain	1.0000
8:27503764:GTA:G	donor_loss	1.0000
8:27503765:T:A	donor_loss	1.0000
8:27506863:T:TA	acceptor_gain	1.0000
8:27506864:G:A	acceptor_gain	1.0000
8:27518030:A:AG	acceptor_gain	1.0000
8:27518036:A:AG	acceptor_gain	1.0000
8:27518037:G:GG	acceptor_gain	1.0000
8:27518037:GAA:G	acceptor_gain	1.0000
8:27538745:G:T	donor_gain	1.0000
8:27541459:T:A	acceptor_gain	1.0000
8:27543743:CCCCA:C	acceptor_loss	1.0000
8:27543744:CCCAG:C	acceptor_loss	1.0000
8:27543745:CCAG:C	acceptor_loss	1.0000

AlphaMissense

3676 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:27515802:T:A	W274R	0.996
8:27515802:T:C	W274R	0.996
8:27522454:A:T	D335V	0.996
8:27525372:A:C	S357R	0.996
8:27525374:T:A	S357R	0.996
8:27525374:T:G	S357R	0.996
8:27541493:G:C	R467P	0.995
8:27515781:T:C	F267L	0.994
8:27515783:T:A	F267L	0.994
8:27515783:T:G	F267L	0.994
8:27522474:T:A	W342R	0.991
8:27522474:T:C	W342R	0.991
8:27543785:G:C	D496H	0.991
8:27544475:T:A	W541R	0.990
8:27544475:T:C	W541R	0.990
8:27522455:C:A	D335E	0.989
8:27522455:C:G	D335E	0.989
8:27525370:C:A	A356D	0.989
8:27543765:T:C	L489P	0.988
8:27525369:G:C	A356P	0.987
8:27522448:G:A	G333D	0.985
8:27522454:A:C	D335A	0.985
8:27522456:T:A	W336R	0.985
8:27522456:T:C	W336R	0.985
8:27543771:T:A	V491D	0.985
8:27515804:G:C	W274C	0.984
8:27515804:G:T	W274C	0.984
8:27544225:C:G	H524D	0.983
8:27525380:T:A	N359K	0.982
8:27525380:T:G	N359K	0.982

dbSNP variants (sampled 300 via entrez): RS1000081080 (8:27523385 A>G), RS1000137694 (8:27529347 C>T), RS1000170521 (8:27529611 A>G), RS1000230352 (8:27530497 T>C), RS1000247848 (8:27491010 C>A,G,T), RS1000287698 (8:27515292 G>A,T), RS1000344552 (8:27534677 C>A,T), RS1000391587 (8:27496534 G>A,T), RS1000421781 (8:27523691 A>G), RS1000481380 (8:27491141 G>A,C,T), RS1000501535 (8:27502595 G>A), RS1000502604 (8:27540263 G>A), RS1000552821 (8:27518796 G>A,C), RS1000692867 (8:27508290 C>T), RS1000852319 (8:27502971 C>T)

Disease associations

OMIM: gene MIM:132811 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Disease	Classification	Inheritance
hypercholesterolemia, familial, 1	No Known Disease Relationship	Autosomal dominant

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001677	Coronary artery atherosclerosis
HP:0003141	Increased LDL cholesterol concentration
HP:0010874	Tendon xanthomatosis

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001786_19	Dental caries	4.000000e-07
GCST002539_72	Schizophrenia	2.000000e-08
GCST003043_91	Inflammatory bowel disease	6.000000e-08
GCST003044_18	Crohn’s disease	2.000000e-06
GCST004521_193	Autism spectrum disorder or schizophrenia	3.000000e-09
GCST004744_5	Lung adenocarcinoma	9.000000e-06
GCST004748_131	Lung cancer	2.000000e-08
GCST004749_23	Lung cancer in ever smokers	2.000000e-07
GCST005082_4	Bipolar disorder lithium response (categorical) or schizophrenia	5.000000e-09
GCST006697_22	Parental longevity (combined parental attained age, Martingale residuals)	8.000000e-09
GCST006701_13	Parental longevity (father’s attained age)	2.000000e-07
GCST006803_90	Schizophrenia	8.000000e-12
GCST007603_2	Smoking initiation	2.000000e-12
GCST008810_44	Smoking initiation (ever regular vs never regular)	2.000000e-16
GCST009405_1	Smoking behaviour (cigarettes smoked per day)	6.000000e-13
GCST009407_1	Smoking behaviour (cigarettes smoked per day)	1.000000e-13
GCST009600_146	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-08
GCST011179_3	Cannabis use disorder	3.000000e-09
GCST011179_4	Cannabis use disorder	6.000000e-09
GCST011703_85	Smoking initiation	2.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007796	parental longevity
EFO:0005670	smoking initiation
EFO:0006525	cigarettes per day measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2409 (SINGLE PROTEIN), CHEMBL4523609 (PROTEIN FAMILY), CHEMBL6195534 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195543 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,326,354 (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
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1358	FULVESTRANT	4	56,655
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL93	ZILEUTON	4	21,372
CHEMBL226335	RUTIN	3	57,988
CHEMBL23393	SODIUM LAURYL SULFATE	3	864,340
CHEMBL50	QUERCETIN	3	74,559
CHEMBL51085	EBSELEN	3	13,237
CHEMBL1076347	TRICLOCARBAN	2	15,622
CHEMBL152067	TALINOLOL	2	3,119
CHEMBL169	URSOLIC ACID	2	20,825
CHEMBL250450	ISOQUERCETIN	2	1,626
CHEMBL3818875	GSK2256294	2	137
CHEMBL436774	AR9281	2	137
CHEMBL59356	ATRELEUTON	2	170
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL184238	URB-597	1	417

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs59724122	Efficacy	3	lithium	Bipolar Disorder

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs59724122	EPHX2	3	0.00	1	lithium

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (14 total), top 14:

Ligand	Action	Affinity	Parameter
compound G1 [PMID: 36689364]	Inhibition	10.3	pIC50
EC5026	Inhibition	10.3	pKi
inhibitor M9 [PMID: 38236416]	Inhibition	8.7	pIC50
MPPA	Inhibition	8.68	pIC50
dual sEH/FAAH inhibitor 11	Inhibition	8.3	pIC50
BI-1935	Inhibition	8.15	pIC50
AR-9281	Inhibition	8.1	pIC50
diflapolin	Inhibition	7.7	pIC50
triple modulator 10 [PMID: 29878767]	Inhibition	7.37	pIC50
GSK2256294	Inhibition	6.96	pIC50
SWE101	Inhibition	6.52	pKd
PF750	Inhibition	6.19	pIC50
zafirlukast	Inhibition	5.7	pIC50
oxaprozin	Inhibition	5.3	pIC50

Binding affinities (BindingDB)

1058 measured of 1122 human assays (1123 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[1-[1-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea	KI	0.05 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-[1-(2-methylbutanoyl)piperidin-4-yl]urea	KI	0.06 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[3-fluoro-4-(trifluoromethyl)phenyl]-3-[1-[1-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]urea	KI	0.08 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
5-[4-((R)-2-Hydroxy-propionyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid-trifluoromethoxy-benzylamide	IC50	0.122 nM	US-9776991: Thienomethylpiperazine derivatives as inhibitors of soluble epoxide hydrolase
1-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-[3-fluoro-4-(trifluoromethoxy)phenyl]urea	KI	0.15 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
5-[4-(Pyridine-3-carbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid 2-trifluoromethyl-benzylamide	IC50	0.168 nM	US-9776991: Thienomethylpiperazine derivatives as inhibitors of soluble epoxide hydrolase
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea	KI	0.19 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[1-(2-methylfuran-3-carbonyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea	KI	0.22 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea	KI	0.22 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[1-(3-methylfuran-2-carbonyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea	KI	0.26 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-[1-(2-methylpropanoyl)piperidin-4-yl]urea	KI	0.31 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[1-(2-methylpropanoyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea	KI	0.31 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[1-(furan-3-carbonyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea	KI	0.33 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[3-fluoro-4-(trifluoromethyl)phenyl]-3-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]urea	KI	0.37 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
1-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-[3-fluoro-4-(trifluoromethyl)phenyl]urea	KI	0.38 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
ethyl 4-[[3-fluoro-4-(trifluoromethyl)phenyl]carbamoylamino]piperidine-1-carboxylate	KI	0.38 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
CHEMBL3263289	IC50	0.4 nM
1-(3,5-Dichlorophenyl)-3-(1-propionylpiperidin-4-yl)urea	IC50	0.4 nM	US-9296693: Acyl piperidine inhibitors of soluble epoxide hydrolase
1-(4-Perfluoroisopropylphenyl)-3-(1-propionylpiperidin-4-yl)urea	IC50	0.4 nM	US-9296693: Acyl piperidine inhibitors of soluble epoxide hydrolase
1-(1-(Cyclopropanecarbonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea	IC50	0.4 nM	US-9296693: Acyl piperidine inhibitors of soluble epoxide hydrolase
1-(1-(Trifluoroacetyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea	IC50	0.4 nM	US-9296693: Acyl piperidine inhibitors of soluble epoxide hydrolase
1-(1-(Ethylsulfonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea	IC50	0.4 nM	US-9296693: Acyl piperidine inhibitors of soluble epoxide hydrolase
1-(1-Tosylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea	IC50	0.4 nM	US-9296693: Acyl piperidine inhibitors of soluble epoxide hydrolase
CHEMBL1817677	IC50	0.4 nM
CHEMBL1818386	IC50	0.4 nM
CHEMBL1818385	IC50	0.4 nM
CHEMBL3222130	IC50	0.4 nM
CHEMBL4454212	IC50	0.4 nM
CHEMBL4641404	IC50	0.4 nM
CHEMBL4643551	IC50	0.4 nM
CHEMBL4869434	IC50	0.4 nM
CHEMBL4872738	IC50	0.4 nM
CHEMBL5177544	IC50	0.4 nM
CHEMBL5208857	IC50	0.4 nM
CHEMBL5180183	IC50	0.4 nM
5-{4-[2-(2-Chloro-phenyl)-acetyl]-piperazin-1-ylmethyl}-thiophene-2-carboxylic acid 2-trifluoromethyl-benzylamide	IC50	0.407 nM	US-9776991: Thienomethylpiperazine derivatives as inhibitors of soluble epoxide hydrolase
5-[4-((1R,2R)-2-Phenyl-cyclopropane-carbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid (3-methyl-butyl)-amide	IC50	0.432 nM	US-9776991: Thienomethylpiperazine derivatives as inhibitors of soluble epoxide hydrolase
1-[3-fluoro-4-(trifluoromethyl)phenyl]-3-[1-(2-methylpropanoyl)piperidin-4-yl]urea	KI	0.49 nM	US-10377744: Potent soluble epdxide hydrolase inhibitors
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]cyclohexyl]oxybenzoic acid	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
N-methyl-4-[4-[[4-(trifluoromethoxy)phenyl]carbamoylamino]cyclohexyl]oxybenzamide	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]cyclohexyl]oxy-N-methylbenzamide	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]cyclohexyl]oxy-N-methylpyridine-2-carboxamide	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
tert-butyl 5-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]cyclohexyl]oxypyridine-2-carboxylate	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
tert-butyl 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]cyclohexyl]oxypyridine-2-carboxylate	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]cyclohexyl]oxy-N,N-diethylpyridine-2-carboxamide	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
N,N-diethyl-4-[4-[[4-(trifluoromethoxy)phenyl]carbamoylamino]cyclohexyl]oxypyridine-2-carboxamide	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
1-[4-[[2-(pyrrolidine-1-carbonyl)-4-pyridinyl]oxy]cyclohexyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors
1-[4-(4-cyanophenoxy)cyclohexyl]-3-[4-(trifluoromethyl)phenyl]urea	IC50	0.5 nM	US-9029401: Sorafenib derivatives as sEH inhibitors

ChEMBL bioactivities

3215 potent at pChembl≥5 of 3399 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.02	nM	CHEMBL3327073
10.57	IC50	0.027	nM	GSK2256294
10.55	IC50	0.028	nM	GSK2256294
10.52	IC50	0.03	nM	CHEMBL5190894
10.52	IC50	0.03	nM	CHEMBL6177252
10.52	IC50	0.03	nM	GSK2256294
10.30	IC50	0.05	nM	CHEMBL5425833
10.30	Ki	0.05	nM	CHEMBL5891245
10.30	Ki	0.05	nM	CHEMBL5746598
10.22	Ki	0.06	nM	CHEMBL6038062
10.10	Ki	0.08	nM	CHEMBL4752831
10.09	IC50	0.082	nM	CHEMBL4745610
10.00	IC50	0.1	nM	CHEMBL4781218
10.00	IC50	0.1	nM	CHEMBL566648
9.96	IC50	0.11	nM	CHEMBL5564589
9.91	IC50	0.122	nM	CHEMBL5745591
9.90	IC50	0.125	nM	CHEMBL3104615
9.85	IC50	0.14	nM	CHEMBL5428998
9.85	IC50	0.14	nM	CHEMBL5403016
9.85	EC50	0.14	nM	CHEMBL556717
9.82	Ki	0.15	nM	CHEMBL4748112
9.78	IC50	0.168	nM	CHEMBL5871215
9.74	IC50	0.18	nM	CHEMBL5590604
9.72	Ki	0.19	nM	CHEMBL3327078
9.70	IC50	0.2	nM	CHEMBL2436573
9.70	IC50	0.2	nM	CHEMBL2436575
9.70	IC50	0.2	nM	CHEMBL2436579
9.70	IC50	0.2	nM	CHEMBL6170135
9.70	IC50	0.2	nM	CHEMBL6176852
9.70	IC50	0.2	nM	CHEMBL6175369
9.70	IC50	0.2	nM	CHEMBL6168778
9.70	IC50	0.2	nM	CHEMBL6169258
9.70	IC50	0.2	nM	CHEMBL4211919
9.70	IC50	0.2	nM	CHEMBL6190185
9.66	Ki	0.22	nM	CHEMBL3327067
9.66	Ki	0.22	nM	CHEMBL4781745
9.66	Ki	0.22	nM	CHEMBL4740401
9.64	Ki	0.23	nM	CHEMBL3325465
9.64	IC50	0.23	nM	CHEMBL5573866
9.62	IC50	0.24	nM	CHEMBL6091897
9.60	IC50	0.25	nM	CHEMBL4759847
9.60	IC50	0.25	nM	CHEMBL5435879
9.60	IC50	0.25	nM	CHEMBL5570637
9.60	IC50	0.25	nM	CHEMBL5571161
9.60	EC50	0.25	nM	CHEMBL592741
9.59	Ki	0.26	nM	CHEMBL4764213
9.55	IC50	0.28	nM	CHEMBL5430146
9.55	IC50	0.28	nM	CHEMBL2397148
9.55	IC50	0.28	nM	CHEMBL5406085
9.55	IC50	0.28	nM	CHEMBL5429256

PubChem BioAssay actives

2628 with measured affinity, of 3803 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
1-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-3-[1-(2-methylbutanoyl)piperidin-4-yl]urea	1186229: Inhibition of human recombinant soluble epoxide hydrolase by FRET-based ACPU displacement assay	ki	<0.0001	uM
1-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-3-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]urea	1186229: Inhibition of human recombinant soluble epoxide hydrolase by FRET-based ACPU displacement assay	ki	<0.0001	uM
N-(4-chlorophenyl)-4-[(4-chlorophenyl)carbamoyl-(2-pyrrolidin-1-ylethyl)amino]-3-methylbenzamide	1873510: Inhibition of sEH (unknown origin)	ic50	<0.0001	uM
cis-(1R,3S)-N-[[4-cyano-2-(trifluoromethyl)phenyl]methyl]-3-[[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino]cyclohexane-1-carboxamide	1480235: Inhibition of recombinant human sEH using MNPC as substrate by fluorescence-based assay	ic50	<0.0001	uM
1-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-[3-fluoro-4-(trifluoromethoxy)phenyl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0001	uM
ethyl 4-[[3-fluoro-4-(trifluoromethoxy)phenyl]carbamoylamino]piperidine-1-carboxylate	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0001	uM
1-[3-fluoro-4-(trifluoromethyl)phenyl]-3-[1-[1-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0001	uM
1-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-[1-[1-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0001	uM
3-(4-chlorophenyl)-1-[2-[(4-chlorophenyl)carbamoylamino]-1,3-benzothiazol-6-yl]-1-(2-morpholin-4-ylethyl)urea	1706963: Inhibition of recombinant human sEH using PHOME as substrate measured after 15 mins by fluorescence assay	ic50	0.0001	uM
N-[6-[(4-chlorophenyl)carbamoyl-(2-morpholin-4-ylethyl)amino]-1,3-benzothiazol-2-yl]-2-phenylacetamide	1706963: Inhibition of recombinant human sEH using PHOME as substrate measured after 15 mins by fluorescence assay	ic50	0.0001	uM
4-cyano-N-[(3S)-3-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)propyl]benzamide	431445: Inhibition of human soluble epoxide hydrolase in human HepG cells assessed as conversion of epoxyeicosatienoic acid to dihydroxyeicosatrienoic acid after 30 mins by ELISA	ec50	0.0001	uM
1-[(3S,5R)-3,5-dimethyl-1-adamantyl]-3-[2-fluoro-4-[[3-(4-propanoyl-1,4-diazepane-1-carbonyl)piperidin-1-yl]methyl]phenyl]urea	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0001	uM
N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-1-[[4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorophenyl]methyl]piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0001	uM
1-[[4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorophenyl]methyl]piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0001	uM
(3S)-1-[4-[(3,5-dimethyl-1-adamantyl)carbamoylamino]benzoyl]-N-[3-(hydroxyamino)-3-oxopropyl]piperidine-3-carboxamide	2099197: Inhibition of recombinant human sEH using PHOME as substrate preincubated for 10 mins followed by substrate addition by fluorescence based assay	ic50	0.0001	uM
N-[[4-bromo-2-(trifluoromethoxy)phenyl]methyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide	446441: Inhibition of soluble EH in human HepG2 cells by cellular assay	ic50	0.0001	uM
9-(2,6-difluorobenzoyl)-N-[4-(trifluoromethoxy)phenyl]-2,9-diazaspiro[5.5]undecane-2-carboxamide	1064059: Inhibition of human recombinant sEH expressed in baculovirus infected insect Sf9 cells using cyano(6-methoxynaphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl] carbonate as substrate preincubated for 30 mins followed by substrate addition measured after 20 to 45 mins by fluorescence assay	ic50	0.0001	uM
1-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0001	uM
1-[1-(3-methylfuran-2-carbonyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0002	uM
1-(4-ethylcyclohexyl)-3-[1-(2-methylbutanoyl)piperidin-4-yl]urea	1186229: Inhibition of human recombinant soluble epoxide hydrolase by FRET-based ACPU displacement assay	ki	0.0002	uM
(3S)-1-[3-fluoro-4-[[3-fluoro-4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]sulfonyl-N-[3-(hydroxyamino)-3-oxopropyl]piperidine-3-carboxamide	2099197: Inhibition of recombinant human sEH using PHOME as substrate preincubated for 10 mins followed by substrate addition by fluorescence based assay	ic50	0.0002	uM
(3S)-1-[4-[(3,5-dimethyl-1-adamantyl)carbamoylamino]-3-fluorophenyl]sulfonylpiperidine-3-carboxamide	2099197: Inhibition of recombinant human sEH using PHOME as substrate preincubated for 10 mins followed by substrate addition by fluorescence based assay	ic50	0.0002	uM
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea	1186229: Inhibition of human recombinant soluble epoxide hydrolase by FRET-based ACPU displacement assay	ki	0.0002	uM
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea	1186229: Inhibition of human recombinant soluble epoxide hydrolase by FRET-based ACPU displacement assay	ki	0.0002	uM
8-(2-fluoro-5-hydroxybenzoyl)-N-[4-(trifluoromethoxy)phenyl]-2,8-diazaspiro[4.5]decane-2-carboxamide	775173: Inhibition of human recombinant sEH using cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl]carbonate after 20 to 45 mins by fluorescence assay	ic50	0.0002	uM
8-(quinoline-5-carbonyl)-N-[4-(trifluoromethoxy)phenyl]-2,8-diazaspiro[4.5]decane-2-carboxamide	775173: Inhibition of human recombinant sEH using cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl]carbonate after 20 to 45 mins by fluorescence assay	ic50	0.0002	uM
8-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-N-[4-(trifluoromethoxy)phenyl]-2,8-diazaspiro[4.5]decane-2-carboxamide	775173: Inhibition of human recombinant sEH using cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl]carbonate after 20 to 45 mins by fluorescence assay	ic50	0.0002	uM
1-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-[1-(2-methylpropanoyl)piperidin-4-yl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0003	uM
1-[1-(3-methylfuran-2-carbonyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea	1698381: Inhibition of recombinant human sEH expressed in baculovirus expression system assessed as reduction in ACPU binding incubated for 1 hr by FRET displacement assay	ki	0.0003	uM
1-(2-amino-1,3-benzothiazol-6-yl)-3-(3-bromo-4-fluorophenyl)-1-(2-morpholin-4-ylethyl)urea	1706963: Inhibition of recombinant human sEH using PHOME as substrate measured after 15 mins by fluorescence assay	ic50	0.0003	uM
(3S)-1-[3-fluoro-4-[[4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]sulfonyl-N-[3-(hydroxyamino)-3-oxopropyl]piperidine-3-carboxamide	2099197: Inhibition of recombinant human sEH using PHOME as substrate preincubated for 10 mins followed by substrate addition by fluorescence based assay	ic50	0.0003	uM
4-[4-[[4-(trifluoromethoxy)phenyl]carbamoylamino]cyclohexyl]oxybenzoic acid	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
N-(4-chlorophenyl)-4-[(4-chlorophenyl)carbamoyl-[2-(3-oxomorpholin-4-yl)ethyl]amino]-3-methylbenzamide	1873510: Inhibition of sEH (unknown origin)	ic50	0.0003	uM
N-(1,3-benzodioxol-5-yl)-4-[(4-chlorophenyl)carbamoyl-[2-(2-oxopyrrolidin-1-yl)ethyl]amino]-3-methylbenzamide	1873510: Inhibition of sEH (unknown origin)	ic50	0.0003	uM
1-[4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorobenzoyl]-N-(2-hydroxyethyl)piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
N-(1,3-dihydroxypropan-2-yl)-1-[[4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorophenyl]methyl]piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[[4-[[(3R,5S)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorophenyl]methyl]-N-(2-hydroxypropyl)piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
N-[4-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]carbamoyl]cyclohexyl]-4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorobenzamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorobenzoyl]-N,N-diethylpiperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[4-[[(3R,5S)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorobenzoyl]-N-(2-hydroxypropyl)piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[[4-[[(3S,5R)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorophenyl]methyl]-N,N-bis(2-hydroxyethyl)piperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[(3R,5S)-3,5-dimethyl-1-adamantyl]-3-[2-fluoro-4-[[4-[2-(1-propanoylpiperidin-4-yl)acetyl]-1,4-diazepan-1-yl]methyl]phenyl]urea	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[[4-[[(3R,5S)-3,5-dimethyl-1-adamantyl]carbamoylamino]-3-fluorophenyl]methyl]-N,N-diethylpiperidine-3-carboxamide	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
1-[(3S,5R)-3,5-dimethyl-1-adamantyl]-3-[2-fluoro-4-[[3-[4-(2-methylbutanoyl)-1,4-diazepane-1-carbonyl]piperidin-1-yl]methyl]phenyl]urea	2027047: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0003	uM
methyl 3-[[(3R)-1-[3-fluoro-4-[[4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]sulfonylpiperidine-3-carbonyl]amino]propanoate	2099197: Inhibition of recombinant human sEH using PHOME as substrate preincubated for 10 mins followed by substrate addition by fluorescence based assay	ic50	0.0003	uM
N-[3-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)propyl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide	431445: Inhibition of human soluble epoxide hydrolase in human HepG cells assessed as conversion of epoxyeicosatienoic acid to dihydroxyeicosatrienoic acid after 30 mins by ELISA	ec50	0.0003	uM
4-cyano-N-[3-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)propyl]benzamide	431445: Inhibition of human soluble epoxide hydrolase in human HepG cells assessed as conversion of epoxyeicosatienoic acid to dihydroxyeicosatrienoic acid after 30 mins by ELISA	ec50	0.0003	uM
N-[(2,4-dichlorophenyl)methyl]-4-(3-methylsulfonylphenoxy)piperidine-1-carboxamide	453481: Inhibition of human soluble epoxide hydrolase in human HepG cells assessed as conversion of epoxyeicosatienoic acid to dihydroxyeicosatrienoic acid after 30 mins by ELISA	ec50	0.0003	uM
N-[(2,4-dichlorophenyl)methyl]-4-[4-(methylcarbamoyl)phenoxy]piperidine-1-carboxamide	453481: Inhibition of human soluble epoxide hydrolase in human HepG cells assessed as conversion of epoxyeicosatienoic acid to dihydroxyeicosatrienoic acid after 30 mins by ELISA	ec50	0.0003	uM
N-[(2,4-dichlorophenyl)methyl]-4-[4-(methylsulfamoyl)phenoxy]piperidine-1-carboxamide	453481: Inhibition of human soluble epoxide hydrolase in human HepG cells assessed as conversion of epoxyeicosatienoic acid to dihydroxyeicosatrienoic acid after 30 mins by ELISA	ec50	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	6
sodium arsenite	increases expression, decreases expression, decreases reaction, affects methylation, affects cotreatment (+1 more)	5
bisphenol A	affects cotreatment, increases methylation, decreases expression, affects expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation, affects expression	3
methylmercuric chloride	decreases expression, increases expression	2
pirinixic acid	affects binding, decreases expression, increases activity, affects expression	2
Resveratrol	affects cotreatment, increases expression	2
Zoledronic Acid	decreases expression, increases expression	2
Air Pollutants	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
bufotalin	decreases expression	1
methyleugenol	decreases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
pyrithione zinc	increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
5-hydroxy-6,8,11,14-eicosatetraenoic acid	increases activity	1
15-hydroxy-5,8,11,13-eicosatetraenoic acid	increases activity	1
cerous chloride	affects expression, affects cotreatment, increases expression	1
lanthanum chloride	increases expression, affects cotreatment	1
chlorobenzene	decreases expression	1
naphthalene	increases expression	1

ChEMBL screening assays

314 unique, capped per target: 311 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001508	Binding	Inhibition of human soluble epoxide hydrolase	Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors. — Bioorg Med Chem Lett
CHEMBL4312974	ADMET	Substrate activity at sEH in human liver cytosol assessed as diol release by UPLC-Q-TOF/MS analysis	Hip To Be Square: Oxetanes as Design Elements To Alter Metabolic Pathways. — 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_D1ME	Abcam K-562 EPHX2 KO	Cancer cell line	Female
CVCL_D2IZ	Abcam Raji EPHX2 KO	Cancer cell line	Male
CVCL_UQ46	Abcam Jurkat EPHX2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab