Epoxide Hydrolase

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。

PAL-4刺激 LYPLAL1 的活性, 一种特征不佳的丝氨酸水解酶，与人类代谢特征具有复杂的遗传联系。

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。

SP-C01 是一种具口服活性的可溶性环氧化酶(sEH)抑制剂，同时也是部分过氧化物酶体增生物活化受体γ(PPARγ)的激动剂。SP-C01 能够抑制 Ser273 的磷酸化。

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.

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.

sEH/HDAC6-IN-1 (compound M9) 作为一种口服有效、选择性强的sEH和HDAC6双效抑制剂，其IC50值在 2 nM (human sEH)，0.72 nM (murine sEH) 及 5 nM (HDAC6)。此化合物显示出显著的镇痛及抗炎活性。

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].

PROTACsEH-degrader-3 (Compound 1a) 是一种靶向sEH的PROTAC降解剂，能够专一性地降解胞质内的sEH，而不对过氧化物酶体内的sEH产生影响。它通过CRBN依赖的溶酶体途径降解sEH，而非蛋白酶体途径，其对人sEH的IC50为0.8 nM。该化合物还可抑制内质网应激，适用于研究与内质网应激相关的炎症、代谢疾病。

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。

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。

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。

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。

TPPU 是一种可溶性环氧化物水解酶(sEH)抑制剂，对猴子和人类的IC50分别为37和3.7 nM。