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Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 555 | 8p21.2-p21.1 | EPHX2 | epoxide hydrolase 2 | |
Mouse | - | 554 | 14 34.36 cM | Ephx2 | epoxide hydrolase 2, cytoplasmic | |
Rat | - | 554 | 15p12 | Ephx2 | epoxide hydrolase 2 | |
Gene and Protein Information Comments | ||||||
Three protein isoforms are reported from the human gene, with isoform a (555 amino acids) being the longest. The mouse gene produces 4 transcripts and protein isoforms, isoform a being the longest at 554 amino acids. |
Previous and Unofficial Names ![]() |
epoxide hydrolase 2, cytoplasmic | sEH | soluble epoxide hydrolase | bifunctional epoxide hydrolase 2 |
Database Links ![]() |
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Alphafold | P34913 (Hs), P34914 (Mm), P80299 (Rn) |
BRENDA | 3.1.3.76, 3.3.2.10 |
ChEMBL Target | CHEMBL2409 (Hs), CHEMBL4140 (Mm), CHEMBL5669 (Rn) |
Ensembl Gene | ENSG00000120915 (Hs), ENSMUSG00000022040 (Mm), ENSRNOG00000017286 (Rn) |
Entrez Gene | 2053 (Hs), 13850 (Mm), 65030 (Rn) |
Human Protein Atlas | ENSG00000120915 (Hs) |
KEGG Enzyme | 3.1.3.76, 3.3.2.10 |
KEGG Gene | hsa:2053 (Hs), mmu:13850 (Mm), rno:65030 (Rn) |
OMIM | 132811 (Hs) |
Pharos | P34913 (Hs) |
RefSeq Nucleotide | NM_001979 (Hs), NM_007940 (Mm), NM_022936 (Rn) |
RefSeq Protein | NP_001970 (Hs), NP_031966 (Mm), NP_075225 (Rn) |
UniProtKB | P34913 (Hs), P34914 (Mm), P80299 (Rn) |
Wikipedia | EPHX2 (Hs) |
Enzyme Reaction ![]() |
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific inhibitor tables |
Immunopharmacology Comments |
Its role in metabolism of arachadonic acid EET metabolites, means that sEH participates in the regulation of prostaglandin and leukotriene production and therefore in immune homeostasis. Small molecule sEH inhibitors can be used as chemical probes to investigate EET (immuno)biology [18]. |
Immuno Process Associations | ||
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Biologically Significant Variants ![]() |
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General Comments |
Epoxide hydrolase 2 (sEH) performs two enzymatic functions. The C terminal contains an epoxide hydrolase domain and the N terminal has a lipid phosphatase domain [19]. sEH plays a major role in the metabolism of endogenous chemical mediators originated from arachidonic acid, including epoxyeicosatrienoic acids (EETs, which are arachidonic acid metabolites produced by certain Cyp450 enzymes) and squalene oxide (a key intermediate in cholesterol biosynthesis). Through metabolism of EETs and other lipid mediators, sEH plays a role in several pathologies, including hypertension, cardiac hypertrophy, and arteriosclerosis [12]. It also appears to be involved in pain mechanisms. Inhibition of sEH is expected to increase EETs levels, thereby potentiating their in vivo anti-inflammatory and vasodilatory effects. Novel drugs targeting sEH have progressed to clinical trial for inflammatory and cardiovascular diseases. |
1. Bellien J, Djerada Z. (2022) Use of inhibitors of phosphatase activity of soluble epoxide for the treatment of cardiometabolic diseases. Patent number: US20220023265A1. Assignee: Universitaire De Reims. Priority date: 16/09/2019. Publication date: 27/01/2022.
2. Blocher R, Lamers C, Wittmann SK, Diehl O, Hanke T, Merk D, Steinhilber D, Schubert-Zsilavecz M, Kahnt AS, Proschak E. (2016) Design and synthesis of fused soluble epoxide hydrolase/peroxisome proliferator-activated receptor modulators. Medchemcomm, 7: 1209-1216. DOI: 10.1039/C6MD00042H
3. Blöcher R, Wagner KM, Gopireddy RR, Harris TR, Wu H, Barnych B, Hwang SH, Xiang YK, Proschak E, Morisseau C et al.. (2018) Orally Available Soluble Epoxide Hydrolase/Phosphodiesterase 4 Dual Inhibitor Treats Inflammatory Pain. J Med Chem, 61 (8): 3541-3550. [PMID:29614224]
4. Chen Y, Chen L, Xu H, Cao R, Morisseau C, Zhang M, Shi Y, Hammock BD, Wang J, Zhuang J et al.. (2023) Structure-Directed Discovery of Potent Soluble Epoxide Hydrolase Inhibitors for the Treatment of Inflammatory Diseases. J Med Chem, 66 (4): 2979-3009. [PMID:36689364]
5. Chen Y, Sun J, Tong H, Wang J, Cao R, Xu H, Chen L, Morisseau C, Zhang M, Shi Y et al.. (2024) Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality. J Med Chem, 67 (3): 2095-2117. [PMID:38236416]
6. Codony S, Pujol E, Pizarro J, Feixas F, Valverde E, Loza MI, Brea JM, Saez E, Oyarzabal J, Pineda-Lucena A et al.. (2020) 2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors: In Vivo Evaluation in a Murine Model of Acute Pancreatitis. J Med Chem, 63 (17): 9237-9257. [PMID:32787085]
7. Du F, Sun W, Morisseau C, Hammock BD, Bao X, Liu Q, Wang C, Zhang T, Yang H, Zhou J et al.. (2021) Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis. Eur J Med Chem, 223: 113678. [PMID:34218083]
8. Fornage M, Boerwinkle E, Doris PA, Jacobs D, Liu K, Wong ND. (2004) Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Circulation, 109 (3): 335-9. [PMID:14732757]
9. Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerstmeier J, Liening S, Werner M et al.. (2017) Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase. Sci Rep, 7 (1): 9398. [PMID:28839250]
10. Hammock B, Kodani S. (2017) Inhibitors for soluble epoxide hydrolase (seh) and fatty acid amide hydrolase (faah). Patent number: WO2017160861A1. Assignee: The Regents Of The University Of California. Priority date: 15/03/2016. Publication date: 21/09/2017.
11. Hammock BD, McReynolds CB, Wagner K, Buckpitt A, Cortes-Puch I, Croston G, Lee KSS, Yang J, Schmidt WK, Hwang SH. (2021) Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative. J Med Chem, 64 (4): 1856-1872. [PMID:33550801]
12. Imig JD, Hammock BD. (2009) Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov, 8 (10): 794-805. [PMID:19794443]
13. Jones PD, Tsai HJ, Do ZN, Morisseau C, Hammock BD. (2006) Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett, 16 (19): 5212-6. [PMID:16870439]
14. Klingler FM, Wolf M, Wittmann S, Gribbon P, Proschak E. (2016) Bacterial Expression and HTS Assessment of Soluble Epoxide Hydrolase Phosphatase. J Biomol Screen, 21 (7): 689-94. [PMID:27009944]
15. Kodani SD, Wan D, Wagner KM, Hwang SH, Morisseau C, Hammock BD. (2018) Design and Potency of Dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors. ACS Omega, 3 (10): 14076-14086. DOI: 10.1021/acsomega.8b01625 [PMID:30411058]
16. Kramer JS, Woltersdorf S, Duflot T, Hiesinger K, Lillich FF, Knöll F, Wittmann SK, Klingler FM, Brunst S, Chaikuad A et al.. (2019) Discovery of the First in Vivo Active Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain. J Med Chem, 62 (18): 8443-8460. [PMID:31436984]
17. Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, Hammock BD, Couper DJ, Heiss G, Zeldin DC. (2006) Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet, 15 (10): 1640-9. [PMID:16595607]
18. Morisseau C, Hammock BD. (2013) Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol, 53: 37-58. [PMID:23020295]
19. Newman JW, Morisseau C, Harris TR, Hammock BD. (2003) The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci USA, 100 (4): 1558-63. [PMID:12574510]
20. Schierle S, Flauaus C, Heitel P, Willems S, Schmidt J, Kaiser A, Weizel L, Goebel T, Kahnt AS, Geisslinger G et al.. (2018) Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology. J Med Chem, 61 (13): 5758-5764. [PMID:29878767]
21. Taylor SJ, Soleymanzadeh F, Eldrup AB, Farrow NA, Muegge I, Kukulka A, Kabcenell AK, De Lombaert S. (2009) Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett, 19 (20): 5864-8. [PMID:19758802]