Last update 01 Nov 2024

mEH

Last update 01 Nov 2024

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).

Drugs associated with mEH

JP2023011148

Patent Mining

Target

mEH

Mechanism-

Active Org.

Saga University

Originator Org.

Saga University

Active Indication

Cardiovascular Diseases

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

1,235

Literatures (Medical) associated with mEH

01 Oct 2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Mitigation of gestational diabetes-induced endothelial dysfunction through FGF21-NRF2 pathway activation involving L-Cystine

Article

Author: Lai, Yanan ; Li, Xiaoqing ; Zhang, Hongping ; Zheng, Zhenzhen ; Huang, Huiya ; Chen, Kaixin ; Wang, Linlin ; Zheng, Jianqiong ; Sun, Congcong ; Xu, Xiaomin ; Wang, Hai ; Chu, Maoping

Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21's impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96 h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via AKT phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDM + ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21's efficacy.

01 Oct 2024·International Journal of Biological Macromolecules

Multifaceted exploration of acylthiourea compounds: In vitro cytotoxicity, DFT calculations, molecular docking and dynamics simulation studies

Article

Author: Arulraj, Arunachalam ; Santibanez, Juan F ; Kokkarachedu, Varaprasad ; Madhavan, Geetha ; Echeverria, Cesar ; Panneerselvam, Murugesan ; Ramirez-Tagle, Rodrigo ; Mangalaraja, Ramalinga Viswanathan ; Swaminathan, Srividya ; Moraga, Daniel ; Haribabu, Jebiti ; Dasararaju, Gayathri

This study reports the synthesis and analysis of biologically active acylthiourea compounds (1 and 2) with a cyclohexyl moiety. The compounds were characterized using UV-Visible, FT-IR, ¹H/¹³C NMR, and elemental analysis. The crystal structure of 2 was solved, revealing intra- and inter-molecular hydrogen bonds. Density functional theory (DFT) calculations provided insights into chemical reactivity and non-covalent interactions. Cytotoxicity assays showed the cyclohexyl group enhanced the activity of compound 2 compared to compound 1. Epoxide hydrolase 1 was predicted as the enzyme target for both compounds. We modeled the structure of epoxide hydrolase 1 and performed molecular dynamics simulation and docking studies. Additionally, in silico docking with SARS-CoV-2 main protease, human ACE2, and avian influenza H5N1 hemagglutinin indicated strong binding potential of the compounds. This integrated approach improves our understanding of the biological potential of acylthiourea derivatives.

01 Sep 2024·Biochemical and Biophysical Research Communications

Inhibition of soluble epoxide hydrolase by natural isothiocyanates

Article

Author: Taylor, Jonathan ; Yee, Baily ; Espiritu, Michael J ; Elbarbry, Fawzy ; Soo, Kaylen

GOALThe long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors.METHODSMolecular docking was used to model likely interactions between the ligands and receptors. The sEH inhibitory activity was tested using a validated fluorescence-based assay and PHOME as a substrate. To evaluate their selectivity as sEH inhibitors, the inhibitory potential of the ITCs was determined on microsomal epoxide hydrolase (mEH) and cytochrome P450 (CYP) enzymes in human liver microsomes. Probe substrates such as styrene oxide (mEH substrate) and established substrates for CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were used in this study. The metabolites of these substrates were analyzed using validated LC-MS/MS and HPLC-UV assays.RESULTSMolecular Docking revealed significant differences in binding site preference among the ITCs in silico and pointed to important interactions between the ligands and the catalytic residues of the sEH enzyme. In vitro, the ITCs showed varying degrees of sEH inhibition, but sulforaphane (SFN) and phenyl isothiocyanate (PITC) were the most potent inhibitors with IC₅₀ values of 3.65 and 7.5 μM, respectively. mEH was not significantly inhibited by any of the ITCs. Erucin and iberin were the only ITCs that did not inhibit the activity of any of the tested CYP enzymes.CONCLUSIONOur results demonstrate that natural ITCs have the potential to offer safe, selective, and potent sEH inhibition.

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mEH

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