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Last update 08 May 2025

mEH

Last update 08 May 2025

Basic Info

Synonyms

EPHX, EPHX1, EPOX

+ [4]

Introduction

Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water (By similarity). Plays a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids (PubMed:22798687). Metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and glycerol (PubMed:24958911). Binds 20(S)-hydroxycholesterol (20(S)-OHC) (By similarity).

Drugs associated with mEH

WS-82

Target

mEH

Mechanism

mEH inhibitors

Active Org.

Beijing Institute of Technology

Originator Org.

Beijing Institute of Technology

Active Indication

Rheumatoid Arthritis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DJ-89

Target

mEH

Mechanism

mEH inhibitors

Active Org.

Beijing Institute of Technology

Originator Org.

Beijing Institute of Technology

Active Indication

Rheumatoid Arthritis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

US20250049736

Patent Mining

Target

mEH

Mechanism

mEH inhibitors

Active Org.

Government of the United States of America

Originator Org.

Government of the United States of America

Active Indication

Cardiovascular Diseases [+5]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with mEH

100 Translational Medicine associated with mEH

0 Patents (Medical) associated with mEH

2,385

Literatures (Medical) associated with mEH

31 Dec 2025·Journal of Enzyme Inhibition and Medicinal Chemistry

Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase

Article

Author: Phong, Nguyen Viet ; Kim, Hyo-Sung ; Yeom, Eunbyul ; Yang, Seo Young ; Zhao, Yan

This study investigated the potential of the indirubin-3'-oxime (I3O) compound to mitigate temperature-induced male infertility in Drosophila melanogaster. Elevated temperatures significantly reduced egg-hatching rates, but I3O supplementation improved these rates, suggesting it can partially restore fertility under heat stress. Additionally, I3O was found to inhibit soluble epoxide hydrolase (sEH), an enzyme involved in the metabolism of epoxyeicosatrienoic acids, which are vital for reproductive health. I3O exhibited sEH inhibitions with an IC₅₀ value of 59.74 ± 0.41 µM. Enzyme kinetics revealed that I3O acts as a non-competitive inhibitor of sEH with a K_i value of 78.88 µM. Molecular docking showed strong interactions between I3O and key residues in the allosteric regions within the sEH enzyme, with a binding affinity of -9.2 kcal/mol. These interactions were supported by 100 ns molecular dynamics simulations, which confirmed the stability of the sEH-I3O complex.

01 Dec 2025·Endocrine Pathology

Identification of Specific Biomarkers for Anaplastic Thyroid Carcinoma Through Spatial Transcriptomic and Immunohistochemical Profiling

Article

Author: Jung, Chan Kwon ; Jeon, Sora ; Bychkov, Andrey ; Mete, Ozgur ; Haq, Faridul

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with a poor prognosis. Despite its rarity, identifying predictive molecular markers that distinguish ATC from follicular cell-derived non-anaplastic thyroid carcinomas is critical for improving diagnosis and treatment strategies. This study aimed to identify and validate key mRNA and protein markers associated with ATC progression and dedifferentiation. We performed spatial transcriptomic analysis on an index case of ATC coexisting with papillary thyroid carcinoma (PTC) and identified eight differentially expressed mRNA markers. These findings were validated in a large cohort using immunohistochemistry on tissue microarrays across various thyroid tumor types, including follicular adenoma, PTC, poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, and ATC. Additionally, the impact of BRAF p.V600E mutation status on these markers was evaluated. COL7A1, LAMC2, SPHK1, and SRPX2 mRNA and protein levels were significantly overexpressed in ATCs. Conversely, CD24, EPHX1, GPX3, and RBM47 mRNA and protein levels were markedly downregulated in ATCs. Functional enrichment analysis, based on mRNA expression data, identified the role of these proteins in tumor invasion, epithelial-mesenchymal transition, extracellular matrix remodeling, and immune evasion. The expression levels of these markers were independent of BRAF p.V600E mutation status, highlighting their potential as diagnostic markers. In summary, this study identified eight molecular markers that can distinguish ATC from other thyroid tumors. The validation of these markers at both the mRNA and protein levels underscores their clinical relevance in ATC diagnosis and tumor characterization. These findings provide a foundation for future biomarker-driven diagnostic and therapeutic strategies for ATC.

01 Dec 2025·Journal of Sport and Health Science

Aerobic exercise alleviates statin-induced PCSK9 upregulation by increasing epoxyeicosatrienoic acid levels through the FoxO3a–Sirt6 axis

Article

Author: Gui, Yajun ; Liu, Leiling ; Hu, Jiahui ; Lei, Hao ; Chen, Jingyuan ; Xu, Danyan ; Sun, Kaijun

BACKGROUNDStatins are the cornerstone of low-density lipoprotein cholesterol (LDL-C)-lowering therapy; however, the therapeutic efficacy of statins in countering atherosclerotic cardiovascular disease (ASCVD) is compromised by the concurrent elevation of proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal molecule that increases LDL-C levels. Aerobic exercise lowers PCSK9 levels, but the underlying mechanism remains unclear. Therefore, we investigated how aerobic exercise can ameliorate statin-induced increases in PCSK9 levels.METHODSThree-week-old male American Institute of Cancer Research (ICR) mice were fed a high-fat-cholesterol diet (HFD) for 12 weeks and then administered atorvastatin alone or atorvastatin combined with aerobic exercise (Statin + Ex). Moreover, a total of 165 participants with stable coronary heart disease (CHD) enrolled at the Inpatient and Outpatient Departments of the Second Xiangya Hospital of Central South University, China, from January 2018 to July 2020 were randomized into the Statin group (male/female = 51/33) and Statin + Ex group (male/female = 52/29). Patients in the Statin + Ex group underwent treadmill exercise of 45-60 min/day for 7 days.RESULTSAerobic exercise effectively alleviated statin-induced PCSK9 upregulation in human patients with CHD and hypercholesterolemic ICR mice (all p < 0.05). Mechanistically, our findings revealed that aerobic exercise induced elevated epoxyeicosatrienoic acids (EETs) plasma levels while concurrently reducing the activity of soluble epoxide hydrolase (sEH) (all p < 0.05), an enzyme responsible for EETs degradation. Further, EETs significantly suppressed PCSK9 expression, subsequently reducing the LDL-C levels (all p < 0.05); this effect was mediated via the activation of the forkhead box O3a-silent mating type information regulation 2 homolog 6 (FoxO3a-Sirt6) axis, with no impact on the sterol regulatory element binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase (SREBP2-HMGCR) pathway.CONCLUSIONOur study sheds light on the paradigm of "Exercise is Medicine", providing evidence to support the use of statins combined with exercise in reducing LDL-C levels, and unveils potential avenues for clinical applications of sEH inhibitors, presenting novel prospects for therapeutic interventions in ASCVD.

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mEH

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