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更新于：2025-05-07

EPHX2

更新于：2025-05-07

基本信息

别名

ABHD20、Bifunctional epoxide hydrolase 2、CEH

+ [9]

简介

Bifunctional enzyme (PubMed:12574510). The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides (PubMed:12574510, PubMed:12869654, PubMed:22798687). Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity). Also determines steady-state levels of physiological mediators (PubMed:12574510, PubMed:12869654, PubMed:21217101, PubMed:22798687). Bifunctional enzyme (PubMed:12574510). 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 (PubMed:12574510). Has phosphatase activity toward lyso-glycerophospholipids with also some lower activity toward lysolipids of sphingolipid and isoprenoid phosphates (PubMed:22217705, PubMed:22387545).

关联

项与 EPHX2 相关的药物

TMS-007

靶点

EPHX2 x PLPP

作用机制

EPHX2抑制剂 [+1]

在研机构

箕星药业科技（上海）有限公司 [+2]

原研机构

TMS Co., Ltd.

在研适应症

急性缺血性卒中

非在研适应症-

最高研发阶段临床2/3期

首次获批国家/地区-

首次获批日期1800-01-20

GSK-2256294

靶点

EPHX2

作用机制

EPHX2抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

EC-5026

靶点

EPHX2

作用机制

EPHX2抑制剂

在研机构

Eicosis Human Health, Inc. [+1]

原研机构

University Of California - Davis Branch (513968)

在研适应症

脊髓损伤 [+3]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 EPHX2 相关的临床试验

CTR20250984

/ Recruiting临床2/3期

优化再灌注以改善结局和神经功能（ORION）：一项评价JX10治疗晚时间窗急性缺血性卒中的有效性和安全性的多中心、双盲、安慰剂对照、随机、平行组、2/3期研究

评估AIS发病后4.5至24小时内，符合静脉溶栓条件的患者在标准治疗基础上使用JX10在良好结局方面是否优于安慰剂

开始日期2025-04-02

申办/合作机构

Fuji Yakuhin Co., Ltd.

[+1]

NCT06438471

/ Recruiting临床1期

Development of a Novel Soluble Epoxide Hydrolase Inhibitor As a Strategy for Treating Neuropathic Pain in Patients with SCI

The goal of this clinical trial is to evaluate safety and tolerability of multiple oral doses of EC5026 in male and female patients with neuropathic pain due to spinal cord injury. The main question it aims to answer is whether EC5026 is safe and well tolerated in SCI patients with neuropathic pain. In addition, this trial will also study the effects of EC5026 on pain.
Researchers will compare EC5026 to placebo.
Participants will be asked to:
* Take EC5026 or placebo in a masked fashion, once daily, for 14 consecutive days.
* Undergo physical exams, vital signs assessments, ECGs, and blood draws
* Complete assessments of pain, sleep, functional status, and perception of change

开始日期2025-04-01

申办/合作机构

Eicosis Human Health, Inc.

NCT05764122

/ Withdrawn临床2期

A Multicenter, Operationally Seamless, Double-Blind, Dose-Ranging, Placebo-Controlled, Randomized, Parallel-Group, Phase 2b Study to Evaluate the Efficacy and Safety of Intravenous BIIB131 for Participants With Ischemic Stroke Between 4.5 and 24 Hours After Last Known Well

The primary objective of the study is to evaluate the effects of BIIB131 on arterial revascularization (Part 1) and to determine if BIIB131 improves functional outcome as measured by the Modified Rankin Scale (mRS) when compared with placebo following acute ischemic stroke (AIS) (Part 2). The secondary objectives are to evaluate the effects of BIIB131 on angiographic reperfusion and infarct evolution, to determine if BIIB131 improves functional outcome, pharmacokinetic profile of BIIB131 (Part 1); to evaluate the effects of BIIB131 on acute and 90-day clinical outcomes (Part 2).

开始日期2024-03-29

申办/合作机构

Biogen, Inc.

100 项与 EPHX2 相关的临床结果

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100 项与 EPHX2 相关的转化医学

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0 项与 EPHX2 相关的专利（医药）

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2,910

项与 EPHX2 相关的文献（医药）

2025-12-31·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

作者: 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.

2025-06-01·Biochemistry and Biophysics Reports

Synthesis and evaluation of isoquinolinyl and pyridinyl-based dual inhibitors of fatty acid amide hydrolase and soluble epoxide hydrolase to alleviate orofacial hyperalgesia in the rat

Article

作者: Duong, Leah ; Hammock, Bruce D ; Garcia, Coral ; Salinas, Steve ; Tsang, Amanda ; Gunari, Siena ; Pavana, Lucy ; Mercado, Madison ; Kandasamy, Ram ; Gorostiza, Gabrielle ; Pecic, Stevan ; Gomez, Karen ; Morisseau, Christophe ; Carr, Daniel

The treatment of orofacial pain disorders is poor. Both opioids and serotonin agonists are commonly used; however, they produce dangerous and unpleasant side effects. Therefore, there is an urgent need to identify new pharmacological treatments that can resolve orofacial pain. Moreover, a treatment that engages multiple mechanisms using one compound may be advantageous. Fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) are two enzymes that can regulate both pain and inflammation via independent pathways. Small molecules that inhibit both enzymes simultaneously were previously synthesized and produced antinociception in vivo. Quinolinyl-based dual inhibitors of FAAH and sEH can inhibit acute inflammatory pain in rats. Here, following on these findings, we generated 7 new isoquinolinyl- and 7 pyridinyl-based analogs and tested their inhibition at both enzymes. Structure-activity relationship study coupled with docking experiments, revealed that the isoquinoline moiety is well-tolerated in the binding pockets of both enzymes, yielding several analogs with nanomolar activity in enzymatic assays. All newly synthesized analogs were assessed in the solubility assay at pH 7.4, and we determined that isoquinolinyl- and substituted pyridinyl-analogs exhibit limited solubility under the experimental conditions. The most potent inhibitor, 4f, with IC₅₀ values in the low nanomolar range for both enzymes, was evaluated in a plasma stability assay in human and rat plasma where it showed a moderate stability. Primary binding assays revealed that 4f does not engage any opioid or serotonin receptors. A high dose (3 mg/kg) of 4f reversed orofacial hyperalgesia following pretreatment with nitroglycerin and orofacial injection of formalin; however, this same dose did not inhibit acute orofacial inflammatory pain or restore pain-depressed wheel running. These findings indicate that simultaneous inhibition of FAAH and sEH using isoquinolinyl-based dual inhibitors may only reverse certain components of orofacial hyperalgesia.

2025-06-01·European Journal of Medicinal Chemistry

Phenyl-benzyl-ureas with pyridazinone motif: Potent soluble epoxide hydrolase inhibitors with enhanced pharmacokinetics and efficacy in a paclitaxel-induced neuropathic pain model

Article

作者: Banoglu, Erden ; Çalışkan, Kübra ; Lengerli, Deniz ; Werz, Oliver ; Bakht, Arooj ; Bal, Nur Banu ; Dahlke, Philipp ; Jordan, Paul M ; Çalışkan, Burcu

The severe pain linked to chemotherapy-induced peripheral neuropathy (CIPN) often becomes a critical factor limiting the effective dosage of life-saving chemotherapy treatments. This debilitating side effect not only hampers the effectiveness of cancer therapy but also poses challenges due to the adverse effects of current treatment options for managing CIPN-related pain complications. Soluble epoxide hydrolase (sEH) inhibitors, which elevate endogenous epoxy-fatty acid levels, have been shown to mitigate CIPN-related pain in different rodent models. In our quest to develop potent sEH inhibitors, we developed novel benzyl phenyl urea derivatives incorporating a pyridazinone ring alongside the urea group as a secondary pharmacophore. These compounds demonstrated remarkable potency in inhibiting sEH, with IC₅₀ values ranging from 0.2 to 57 nM. Compound FP9 (IC₅₀ = 0.2 nM), the most potent in this series, exhibited enhanced metabolic stability, translating into significantly improved oral bioavailability (F = 78 %). It consistently relieved pain perception in mice with paclitaxel-induced peripheral neuropathy, achieving a significant and sustained effect compared to gabapentin. In addition, docking studies and molecular dynamics simulations with FP9 provided valuable insights into the binding interactions between the inhibitor and the sEH binding site, offering direction for further optimization of new analogs. These findings align with recent research that highlights the beneficial effects of sEH inhibitors in reducing pain thresholds associated with CIPN.

项与 EPHX2 相关的新闻（医药）

2025-04-04

·药学进展

学科前沿|沈阳药科大学在治疗NASH药物研发方面取得新进展

“点击蓝字关注我们沈阳药科大学在治疗NASH药物研发方面取得新进展 PPS 近日，药物化学领域权威期刊 Journal of Medicinal Chemistry (IF = 6.8)发表了沈阳药科大学陈国良教授/刘中博副教授/徐成副教授课题组在NASH治疗药物研发领域的最新成果。文章题目为“Structure-based design and optimization lead to the identification of novel potent sEH inhibitor with PPARγ partial agonist activity against inflammatory and metabolic-related diseases”。肝脏是药物代谢的主要器官，许多药物都可能导致肝损伤，这也是肝病治疗药物研发面临的重要挑战之一，目前非酒精性脂肪肝炎(NASH)治疗药物极少。研究团队基于前期对可溶性环氧化物水解酶 (sEH)的研究，引入过氧化物酶体增殖物激活受体γ (PPARγ)部分激动片段，设计了一系列双靶标化合物。该研究发现一种新型4-(环己氧基)苯乙酸骨架结构具有PPARγ部分激动活性，并系统研究了其构效关系。同时，通过结构导向的先导化合物优化，开发出口服效果良好的SP-C01——该化合物作为sEH和PPARγ部分激动的双重调节剂，能够抑制PPARγ Ser273磷酸化。体外实验结果显示，其对人源sEH酶的IC50为27 pM，与当前临床最优sEH抑制剂活性水平相当；在糖脂代谢调控方面，其通过sEH抑制与PPARγ/GLUT4信号通路介导的葡萄糖摄取增强效应，在细胞水平呈现出与经典PPARγ激动剂罗格列酮相当的生物活性。实验表明，SP-C01表现出优异的安全性和显著的抗炎镇痛作用，且可逆转或有效阻断NASH及其病程进展，有望成为NASH治疗有效策略。制药工程学院药物化学专业2022级博士研究生曹若琳为文章第一作者，制药工程学院陈国良教授、加州大学戴维斯分校Bruce Hammock院士、药学院刘中博副教授和生命科学与生物制药学院徐成副教授为文章的共同通讯作者，沈阳药科大学为第一通讯单位。该课题得到了国家自然科学基金(项目号82273793)，辽宁省教育厅重点研发项目(项目号LJKZZ20220108)，美国NIEHS RIVER Award R35ES030443，NINDS Counter Act Program U54NS127758，NIEHS/Superfund Research Program P42 ES004699的资助。文章DOI: 10.1021/acs.jmedchem.5c00402文章来源：沈阳药科大学美编排版：杨雨菲文章审核：童景阳杨雨菲罗琪【免责声明】以上内容来源于互联网，不代表本平台立场或观点；如有侵犯作者著作权，请及时与我们联系（Tel：025-83271227，或直接在微信平台留言），我们将及时更正或删除。《药学进展》杂志由国家教育部主管、中国药科大学和中国药学会共同主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

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