soluble epoxide hydrolase

Soluble epoxide hydrolase inhibitor is a soluble epoxide hydrolase inhibitor (human soluble epoxide hydrolase (h-sEH) with pIC50 of 8.4).

Soluble epoxide hydrolase (sEH) PROTAC 1a是一种利用蛋白质降解靶向嵌合体(PROTAC)技术，通过连接区域将cereblon配体1与sEH抑制剂t-TUCB结合。该化合物通过促进sEH的降解，特异性抑制sEH的水解酶活性(IC50 = 0.8 nM)，相较于其磷酸酶活性(IC50 = >10,000 nM)具有较高选择性。sEH PROTAC 1a还特定促进细胞质中而非过氧体中的sEH降解，并通过溶酶体而非蛋白酶体实现其降解。它能够降低thapsigargin诱导的HepG2与293T细胞中磷酸化的inositol-requiring enzyme 1α (IRE1α)水平和X-box结合蛋白1 (XBP1)剪接，表明能减少ER应激。

N,N'-Dicyclohexylurea (AURORA KA-3582) 是一种可溶性环氧化物水解酶 (sEH) 抑制剂。

Dual FAAH/sEH-IN-1 是具有高度亲和力的sEH(可溶性环氧水解酶) (IC50: 9.6 nM) 和FAAH(脂肪酸酰胺水解酶) (IC50: 7 nM) 双重抑制剂，具有抗炎活性。

EC5026 (BPN-19186) 是首创的，非阿片类的，可溶性环氧水解酶 (sEH) 抑制剂，它可有效缓解发炎性和神经性疼痛。

(Rac)-EC5026 ((Rac)-BPN-19186) 是一种有效的可溶性环氧水解酶 (sEH) 哌啶抑制剂，Ki 值为 0.06 nM。(Rac)-EC5026 可用于帕金森氏病和路易体痴呆 (DLB) 的研究。

Diflapolin 是高活性的双 5-脂氧合酶激活蛋白(FLAP) 可溶性环氧化物水解酶抑制剂，具有显著的抗炎作用和较高的靶向选择性。它抑制分离的 sEH 的活性，IC50为20 nM。它还抑制完整人单核细胞和中性粒细胞中 5-LOX 产物的形成，IC50分别为 30 和 170 nM。

AUDA 是可溶性环氧化物水解酶 (sEH) 抑制剂，在小鼠和人 sEH 的IC50分别为 18 和 69 nM，具有抗炎特性。

UC-1728 (t-TUCB) 是一种兔子可溶性环氧化物水解酶抑制剂，兔子肝脏中测得其IC50=2 nM。

AR-9281 (APAU) 是选择性的可溶性环氧化物水解酶抑制剂，可用于研究高血压和 2 型糖尿病。

BI-1935 是可溶性环氧化物水解酶抑制剂，用于与心血管疾病相关的疾病的研究。

1-Cyclohexyl-3-dodecyl urea (NCND) 是高选择性的可溶性环氧化物水解酶 (sEH) 抑制剂，能够增强血管紧张素 II (Ang II) 高血压中的环氧二十碳三烯酸 (EETs) 水平，并降低血压。

N-(3-methoxybenzyl)-octadecanamide 从玛卡 (Lepidium meyenii Walp.) 转化而来。

CUDA 是一种可溶性环氧水解酶抑制剂，对小鼠 sEH 和人 sEH 作用的 IC50分别为 11.1 和 112 nM。它能选择性地上调过氧化物酶体增殖激活受体 PPARα的活性，有用于心血管疾病的研究潜力。

sEH inhibitor-16，作为一种可溶性环氧化物水解酶（sEH）抑制剂，具有2 nM的IC50值。它能够降低小鼠Cerulein诱导的急性胰腺炎（AP）的炎症损伤，适用于免疫炎症研究。

(±)12(13)-DiHOME is the diol form of (±)12(13)-EpOME , a cytochrome P450-derived epoxide of linoleic acid also known as isoleukotoxin. [1] It is formed from 12(13)-EpOME by soluble epoxide hydrolase (sEH) in neutrophils. [2] 12(13)-DiHOME is toxic to Sf21 cells expressing sEH and to lacZ-expressing control cells, unlike isoleukotoxin, which is only toxic to cells containing sEH.[1] [2] Levels of 12(13)-DiHOME are increased in rat spinal cord following burn injury, and it enhances cold tolerance, increases fatty acid uptake into brown adipocytes, and decreases serum triglyceride levels in mice. Levels are also elevated in bronchoalveolar lavage fluid (BALF) in humans following exposure to biodiesel exhaust and in exhaled breath condensate in patients with allergic asthma following allergen exposure.[5] [6] Plasma levels of 12(13)-DiHOME are increased immediately following moderate-intensity exercise in mice and humans, an effect that can be prevented by brown adipose tissue removal in the mouse.[7]

sEH/AChE-IN-3 -15) 是一种有效的、可透过血脑屏障的 sEH(可溶性环氧水解酶)和 AChE(乙酰胆碱酯酶)的双重抑制剂，其 IC50分别为 0.4 nM (hsEH)、1.94 nM (hAChE)、615 (hBChE，丁酰胆碱酯酶)、4.3 nM (msEH) 和 2.61 nM (mAChE)。

sEH inhibitor-1 (compound TCPU ) 是一种有效的、口服具有活力的可溶性环氧化物水解酶 (sEH) 抑制剂，对人和鼠 she 的 IC50 值分别为 0.4 和 5.3 nM。

trans-AUCB (t-AUCB) 是口服具有活力的、选择性的可溶性环氧水解酶 (sEH) 抑制剂，对人，小鼠和大鼠的 sEH 的IC50分别为 1.3 nM，8 nM，8 nM。它具有抗神经胶质瘤特性。

(±)9(10)-DiHOME, the diol derivative of (±)9(10)-EpOME—a cytochrome P450-derived epoxide of linoleic acid also known as leukotoxin—is formed through the action of soluble epoxide hydrolase (sEH) in neutrophils. It exhibits toxicity towards Sf21 cells expressing sEH as well as tolacZ-expressing control cells, differing from leukotoxin which only harms sEH-containing cells. Furthermore, combined exposure to 9(10)- and 12(13)-DiHOME leads to cell death in rabbit renal proximal tubule cells by disrupting mitochondrial respiration, and causes lung injury, respiratory distress, and mortality in mice, highlighting its role as a toxic lipid mediator. Specifically, 9(10)-DiHOME has been associated with acute respiratory distress syndrome (ARDS), a severe and often deadly complication in patients with major burns. Elevated levels of this compound have been detected in the bronchoalveolar lavage fluid (BALF) of women, but not men, with chronic obstructive pulmonary disease (COPD), and its levels are also increased in patients with allergic asthma, indicating its significance in respiratory conditions.

sEH inhibitor-4 (compound B15) has been identified as a potent soluble epoxide hydrolase (SEH) inhibitor with a remarkable inhibitory potency of 0.03 ± 0.01 nm. Intensive structural modification efforts led to the discovery of this compound for its ability to decrease inflammation and alleviate pain in the presence of SEH.

Prostaglandin E2抑制剂3是一种microsomal prostaglandin E合酶-1 (mPGES-1; IC50 = 0.2 µM)的抑制剂，相较于COX-1、COX-2、5-lipoxygenase (5-LO)和soluble epoxide hydrolase (sEH)，在10 µM的无细胞试验中表现出对mPGES-1的选择性。在10 µM和1 µM的浓度下，该抑制剂能抑制A549细胞中IL-1β诱导的PGE2生成以及在J774A.1巨噬细胞中，LPS诱导的IL-6和PGE2生成。同时，它还能抑制由钙离子载体A23187单独或结合花生四烯酸和A23187诱导的5-LO产物形成，包括白三烯B4 (LTB4) 和5-H(p)ETE（IC50s分别为4.9和5.2 µM）。在体内，10 mg/kg剂量的Prostaglandin E2抑制剂3能防止在zymosan诱导的小鼠腹膜炎模型中白细胞渗入腹腔液中。

sEH/AChE-IN-4 -15) 是一种高效穿透血脑屏障的双重抑制剂，针对sEH(可溶性环氧水解酶)和AChE(乙酰胆碱酯酶)，IC50值分别为hsEH 3.1 nM、hAChE 1660 nM、hBChE(丁酰胆碱酯酶) 179 nM、msEH 14.5 nM 以及mAChE 102 nM。

sEH inhibitor-5 是一种 sEH (可溶性环氧化物水解酶) 的有效抑制剂 (IC50: 0.1 nM)。

sEH AChE-IN-1 (Compound 12a) 是一种可溶性环氧化物水解酶 (sEH) 和乙酰胆碱酯酶 (AChE) 的双重抑制剂。sEH AChE-IN-1 具有对抗神经炎症和记忆障碍的累积效应。sEH AChE-IN-1 对阿尔茨海默病 (AD) 表现出研究潜力。

Docosahexaenoic acid is an ω-3 fatty acid that is abundant in the brain and the retina and is known to be important in early development.[1] [2] Maresin 2 (MaR2) is a 13R,14S-dihydroxy DHA formed by recombinant human macrophage 12-lipoxygenase and soluble epoxide hydrolase co-incubated with DHA. [3] At 1 ng/mouse, MaR2 was shown to reduce neutrophil infiltration by 40% in a mouse model of peritonitis, and at 10 pM, MaR2 can enhance human macrophage phagocytosis of zymosan A by 90%. [3] Analytical and biological comparisons of synthetic MaR2 with endogenously derived MaR2 have confirmed its identity as matching the natural product.[4]

sEH inhibitor-2 (化合物 5l) 是一种具有口服活性的可溶性环氧水解酶 (sEH) 抑制剂（IC50= 0.9 nM），预测的口服吸收百分比为71.2-88.4%。sEH inhibitor-2 可使血清中的环氧二十碳三烯酸 (EETs) 保持较高的浓度水平。sEH inhibitor-2 在心血管保护中有研究价值。

Docosahexaenoic acid is the most abundant ω-3 fatty acid in neural tissues, especially in the brain and retina. (±)7(8)-EpDPA is an epoxide derivative of DHA that is generated by the action of cytochrome P450 epoxygenases. It is naturally occurring in plasma and brain and spinal cord tissues and is increased following dietary supplementation with ω-3 fatty acids. (±)7(8)-EpDPA and other epoxy metabolites of DHA modulate receptor and channel activities to evoke diverse effects, such as promoting vasodilation, inhibiting angiogenesis, and decreasing inflammatory and neuropathic pain. (±)7(8)-EpDPA is a substrate of soluble epoxide hydrolase (KM = 15 μM), which converts it to the corresponding diol.

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

SWE101 is a potent human and rat soluble epoxide hydrolase (sEH)-P inhibitor(IC50s of 4 μM and 2.8 μM, respectively).

(±)17(18)-EpETE-Ethanolamide, an ω-3 endocannabinoid epoxide, originates from eicosapentaenoic ethanolamide (EPEA) through cytochrome P450 (CYP) epoxygenases action and is decomposed by soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FA, AH). Its endogenous synthesis occurs in LPS-stimulated and EPEA-supplemented BV-2 microglia cells, a process inhibited by the CYP inhibitor ketoconazole. This compound mitigates IL-6 and nitrite levels while enhancing IL-10 production following LPS exposure in BV-2 microglia. At a dose of 50 µM, it prevents platelet aggregation caused by arachidonic acid but not that triggered by ADP, collagen, or ristocetin. Additionally, it facilitates the dilation of constricted bovine coronary arteries (ED50= 1.1 µM) and blocks VEGF-driven tubulogenesis in human microvascular endothelial cells (HMVECs).

sEH inhibitor-17 (compound 4f) 是一种口服可用的可溶性环氧化物水解酶 (sEH) 抑制剂，抗炎作用显著，其IC50值仅为 2.94 nM。

sEH-IN-1 (example 67) 是一种针对可溶性环氧化物水解酶 (sEH) 的抑制剂，常用于研究由 sEH 介导的各类疾病，如高血压、心血管疾病、炎症及糖尿病等。

sEH-IN-12 is an effective inhibitor of the enzyme soluble epoxide hydrolase (sEH).

Cytochrome P450 metabolism of polyunsaturated fatty acids produces numerous bioactive epoxide regioisomers. (±)13(14)-EpDPA is a docosahexaenoic acid epoxygenase metabolite, derived via epoxidation of the 13,14-double bond of DHA. It has been detected in rat brain and spinal cord and is a preferred substrate for soluble epoxide hydrolase with a Km value of 3.2 μM. (±)13(14)-EpDPA demonstrates antihyperalgesic activity in inflammatory and neuropathic pain models. (±)13(14)-EpDPA and other epoxy metabolites of DHA are also reported to potently inhibit angiogenesis and tumor growth in in vitro assays.

COX-2/sEH-IN-1 是口服具有活力的 COX-2 (IC50: 1.24 μM) 和 sEH (IC50: 0.40 μM) 的双抑制剂，其中sEH 是一种可溶性环氧化物水解酶。COX-2/sEH-IN-1 可以增加抗炎作用、显著降低心血管风险。

Orniplabin, also known as SMTP-7 is a dual inhibitor of thrombolysis and soluble epoxide hydrolase. SMTP-7 promotes thrombolysis and inhibits soluble epoxide hydrolase.

sEH inhibitor-7是一种可溶性环氧化物水解酶（sEH）抑制剂，对人和小鼠的 sEH 有抑制作用，IC 50 s 分别为 6.2 μM 和0.15 μM 。sEH inhibitor-7与抗炎活性分子有关。

10,11-EDT, a substrate for soluble epoxide hydrolase (sEH), is a metabolic derivative of adrenic acid and acts as an endothelium-derived hyperpolarizing factor with potent vasorelaxant effects [1].

Cytochrome P450 metabolism of polyunsaturated fatty acids produces numerous bioactive epoxide regioisomers. (±)10(11)-EpDPA is a docosahexaenoic acid epoxygenase metabolite, derived via epoxidation of the 10,11-double bond of DHA. It has been detected in rat brain and spinal cord, as well as human serum, and acts as a substrate for soluble epoxide hydrolase with a Km value of 5.1 μM. (±)10(11)-EpDPA and other epoxy metabolites of DHA are reported to demonstrate antihyperalgesic activity in inflammatory and neuropathic pain models and to potently inhibit angiogenesis and tumor growth in in vitro assays.

sEH inhibitor-3 是一种可口服且具有选择性和高效性的可溶性环氧化物水解酶 (sEH) 抑制剂，可用于研究癌症。

N-Desbutyl dronedarone is an active metabolite of the antiarrhythmic agent dronedarone .1,2,3It is formed from dronedarone by cytochrome P450s (CYPs) and monoamine oxidase (MAO) in human hepatocyte preparations.4N-Desbutyl dronedarone inhibits the binding of 3,3’,5-triiodo-L-thyronine to the thyroid hormone receptors TRα1and TRβ1(IC50s = 59 and 280 μM for the chicken and human receptors, respectively).1It inhibits CYP2J2-mediated formation of 14,15-EET from arachidonic acid and soluble epoxide hydrolase-mediated formation of 14,15-DHET from 14,15-EET (IC50s = 1.59 and 2.73 μM, respectively, in cell-free assays).2N-Desbutyl dronedarone decreases intracellular ATP levels in H9c2 rat cardiomyocytes (IC50= 1.07 μM) and inhibits mitochondrial complex I, also known as NADH dehydrogenase, and mitochondrial complex II, also known as succinate dehydrogenase, activities in isolated rat heart mitochondria (IC50s = 11.94 and 24.54 μM, respectively).3 1.Van Beeren, H.C., Jong, W.M.C., Kaptein, E., et al.Dronerarone acts as a selective inhibitor of 3,5,3’-triiodothyronine binding to thyroid hormone receptor-α1: in vitro and in vivo evidenceEndocrinology144(2)552-558(2003) 2.Karkhanis, A., Tram, N.D.T., and Chan, E.C.Y.Effects of dronedarone, amiodarone and their active metabolites on sequential metabolism of arachidonic acid to epoxyeicosatrienoic and dihydroxyeicosatrienoic acidsBiochem. Pharmacol.146188-198(2017) 3.Karkhanis, A., Leow, J.W.H., Hagen, T., et al.Dronedarone-induced cardiac mitochondrial dysfunction and its mitigation by epoxyeicosatrienoic acidsToxicol. Sci.163(1)79-91(2018) 4.Klieber, S., Arabeyre-Fabre, C., Moliner, P., et al.Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drugPharmacol. Res. Perspec.2(3)e00044(2014)

Cytochrome P450 metabolites of arachidonic acid, such as 11(12)-EpETrE and 14(15)-EpETrE have been identified as endothelium derived hyperpolarizing factors with vasodilator activity. Soluble epoxide hydrolase (sEH) catalyzes the conversion of EpETrEs to the corresponding DiHETrEs thereby diminishing their activity. Inhibitors of sEH may therefore have clinical utility for treating hypertension and systemic inflammation. S-NEPC is a colorimetric substrate used to measure sEH activity. It also is a substrate for Glutathione S-transferase, microsomal epoxide hydrolase and porcine liver carboxylesterase. Hydrolysis of S-NEPC by sEH yields 4-nitrophenol which can be quantified spectrophotometrically at 405 nm. S-NEPC is adaptable for use in 96-well microwell plate readers.

CAY10640 (sEH inhibitor-1)一种有效的、具有口服活性、可溶于水的环氧化物水解酶 (sEH) 抑制剂，对人和鼠中的sEH 具有抑制作用，IC50s 分别为 0.4 和 5.3 nM。

sEH inhibitor-14 (化合物 33)，一种苯并恶唑酮-5-尿素类似物，是一种效力显著的可溶性环氧化物水解酶 (Epoxide Hydrolase) 抑制剂，具有极低的半抑制浓度 (IC50=0.39 nM)。

TUPS is a selective soluble epoxide hydrolase inhibitor which protects against isoprenaline-induced cardiac hypertrophy.

sEH inhibitor-6 (Compound 3g) is a highly potent soluble epoxide hydrolase (sEH) inhibitor, exhibiting an IC 50 value of 0.5 nM [1].

Murrangatin may be a valuable anti-tumor-promoting agent, it can significantly inhibit Epstein-Barr virus early antigen (EBV-EA) activation, and preserve the high viability of Raji cells, it also exhibits cytotoxicity against cholangiocarcinoma cell line,