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更新于：2025-05-07

mEH

更新于：2025-05-07

基本信息

别名

EPHX、EPHX1、EPOX

+ [4]

简介

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).

关联

项与 mEH 相关的药物

WS-82

靶点

mEH

作用机制

mEH inhibitors

在研机构

北京理工大学

原研机构

北京理工大学

在研适应症

类风湿关节炎

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

DJ-89

靶点

mEH

作用机制

mEH inhibitors

在研机构

北京理工大学

原研机构

北京理工大学

在研适应症

类风湿关节炎

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

US20250049736

专利挖掘

靶点

mEH

作用机制

mEH inhibitors

在研机构

Government of the United States of America

原研机构

Government of the United States of America

在研适应症

心血管疾病 [+5]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 mEH 相关的临床结果

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100 项与 mEH 相关的转化医学

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0 项与 mEH 相关的专利（医药）

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2,385

项与 mEH 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.

2025-12-01·Endocrine Pathology

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

Article

作者: 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.

2025-12-01·Journal of Sport and Health Science

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

Article

作者: 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.

项与 mEH 相关的新闻（医药）

2024-12-31

·今日头条

可克服耐药！哈尔滨医科大学发文：临床治疗胰腺癌有前景的新靶点

【导读】胰腺癌（PC）进展迅速，以吉西他滨为基础的化疗仅带来了有限的疗效。确定关键驱动因素和治疗靶点具有重要的临床价值。 12月30日，哈尔滨医科大学研究团队在期刊《Advanced Science》上发表了研究论文，题为“TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism”，本研究中，研究人员通过综合分析，确定 TRIM21 是一个有前景的驱动介质。本研究进一步对 TRIM21 进行了实验，结果表明 TRIM21 基因敲除在体外和体内均能抑制肿瘤增殖和吉西他滨耐药性。脂质组学分析显示，沉默 TRIM21 可降低花生四烯酸的生成，并抑制铁死亡。鉴于其靶向潜力，本研究筛选出苯扎贝特来阻断 TRIM21 与 EPHX1 的相互作用，并验证了其增敏效果。总之，TRIM21 通过抑制 EPHX1 介导的花生四烯酸代谢促进胰腺癌的生长和吉西他滨耐药性。这为胰腺癌的临床治疗提供了新的有前景的靶点。 https://onlinelibrary.wiley.com/doi/10.1002/advs.202413674 背景信息 01 胰腺癌（PC）是致死率最高的恶性肿瘤之一，5 年生存率约为 10%，死亡率与发病率之比为 94%。以吉西他滨为基础的疗法仍是晚期胰腺癌的首选治疗方案。然而，临床响应率仅为约 20%，总生存期在 6.7 至 10.1 个月之间。胰腺癌的主要驱动基因包括 KRAS（90%）、TP53（71%）、CDKN2A（24%）和 SMAD4（17%）。尽管这些基因已被证实是胰腺癌中的重要驱动基因，但作为临床药物靶点的治疗潜力仍然有限。因此，进一步阐明驱动胰腺癌恶性进展和吉西他滨耐药的关键事件具有重要的临床价值。 TRIM21 是一种 RING 结构域 E3 泛素连接酶，已被证实可参与多种生物学过程，如肿瘤发生、进展和治疗耐药。TRIM21 通过抑制 p62 泛素化，从而降低 Keap1-Nrf2 抗氧化通路的活性，加速肝癌的进展。TRIM21 使 TIF1γ 降解，并促进活性β-连环蛋白的亚细胞转位，从而推动胶质母细胞瘤的进展。此外，TRIM21 还会影响癌症治疗的耐药性。TRIM21 通过降解 VDAC2 抑制 I 型干扰素反应，从而促进对放疗的耐药。TRIM21 抑制胶质瘤细胞衰老，促进恶性表型，并增强替莫唑胺治疗的耐药性。然而，关于 TRIM21 在胰腺癌中的生物学作用和分子机制的报道却十分有限。 EPHX1作为一种保守的生物转化酶，具有解毒功能。EPHX1 通过催化2-AG分解为游离花生四烯酸（AA）和甘油来调节脂质代谢通路。通常，上皮组织中 2-AG 水平升高，会促进肿瘤发生。EPHX1 Tyr113His 多态性导致的酶活性受损是多种肿瘤的高风险因素。同时，AA 介导的脂质过氧化会诱导肿瘤细胞发生铁死亡，并增强抗肿瘤治疗的效果。因此，维持 EPHX1 的活性对于抑制肿瘤进展和提高抗肿瘤疗效至关重要。 TRIM21 在体内和体外促进胰腺癌的增殖 02 为了研究TRIM21 在胰腺癌细胞中的作用，研究人员建立了BXPC3、SW1990 和 Pan02 细胞系的 TRIM21 过表达（TRIM21-OE）模型，以及 SW1990 和 PANC1 细胞系的 TRIM21 基因敲除（TRIM21-KO）模型。随后，通过 CCK8、集落形成和 EdU 染色实验评估了细胞增殖情况。结果表明，TRIM21 过表达可增强 SW1990 和 BXPC3 细胞的增殖（P < 0.0001）。集落形成实验显示，BXPC3-OE 和 SW1990-OE 细胞的集落数量增加（所有 p < 0.05）。EdU 染色实验证实，TRIM21-OE BXPC3 和 SW1990 细胞的 DNA 复制活性更高（所有 p < 0.001）。相反，功能实验表明，SW1990 和 PANC1 细胞中 TRIM21 的缺失会降低细胞增殖（所有 p < 0.0001）、集落形成能力（P < 0.01）和 DNA 复制活性（所有 p < 0.01）。然而，迁移和伤口愈合实验表明，TRIM21-OE 和 TRIM21-KO 对胰腺癌细胞迁移没有显著影响。在 C57BL/6 胰腺癌原位小鼠模型中，感染了 pLV-TRIM21-luc 病毒的 Pan02 细胞表现出比 pLV-control-luc 细胞更强的生物发光强度。并且TRIM21 过表达组的肿瘤体积大于对照组。这些发现进一步证实了 TRIM21 具有癌基因的功能，在体内和体外均能促进 PC 细胞的增殖。 TRIM21 在体内和体外均促进胰腺癌的增殖TRIM21 在体内和体外均促进胰腺癌的增殖 TRIM21 增强胰腺癌对吉西他滨的耐药性 03 为研究 TRIM21 在胰腺癌（PC）吉西他滨耐药中的作用，研究人员建立了吉西他滨耐药胰腺癌细胞系 BXPC3-GR 和 SW1990-GR。研究人员观察到耐药细胞系中 TRIM21 的 mRNA 和蛋白水平升高。接下来，研究人员从 BXPC3-GR 和 SW1990-GR 细胞系中生成了 TRIM21 基因敲除细胞系。集落形成实验表明，TRIM21 沉默增强了吉西他滨对细胞增殖的抑制作用。CCK-8 检测显示，TRIM21 沉默减弱了胰腺癌细胞对吉西他滨的耐药性。Annexin-V/PI 分析表明，与吉西他滨处理的 NC 细胞相比，TRIM21 基因敲除联合吉西他滨处理增加了凋亡和坏死细胞的比例。研究人员还通过凋亡相关蛋白标志物的变化证实了这一点。同样，研究人员发现，在亲代 BXPC3 和 SW1990 细胞中过表达 TRIM21 与 NC 相比，降低了吉西他滨诱导的细胞凋亡。研究人员证明了 PDX#1 和 PDX#2 对吉西他滨治疗表现出耐药性，而 PDX#3 和 PDX#4 对吉西他滨敏感。与 PDX#1 和 PDX#2 相比，PDX#3 和 PDX#4 显示出更显著的肿瘤体积缩小和肿瘤生长抑制指数（TGI）。吉西他滨治疗后，PDX#1 和 PDX#2 肿瘤组织中 KI67 和 PCNA 的表达无差异，而在 PDX#3 和 PDX#4 中，其表达显著降低。结论 04 本研究发现 TRIM21 是胰腺癌进展和吉西他滨耐药的关键驱动因素。TRIM21 通过调节 EPHX1 介导的花生四烯酸代谢，在肿瘤生长和化疗耐药中发挥着关键作用。尤其是，研究人员证明了用苯扎贝特抑制 TRIM21 与 EPHX1 的相互作用，可显著提高胰腺癌细胞对吉西他滨的敏感性。这些发现不仅为提高胰腺癌化疗疗效提供了新的视角，也为克服耐药性提供了有前景的策略。【参考资料】 https://onlinelibrary.wiley.com/doi/10.1002/advs.202413674 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门推荐活动点击免费报名 🕓 线上｜2024年12月6日-2025年1月16日 ▶ 《我的2024》 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会 🕓 上海｜2025年02月28日-03月01日 ▶ 第四届长三角单细胞组学技术应用论坛暨空间组学前沿论坛点击对应文字查看详情

临床1期临床结果