Inhibitors of soluble epoxide hydrolase (sEH) enzymes have shown great potential for the treatment of neuropathic pain. However, current sEH inhibitors have poor physicochemical properties and has not been proven to be safe for human treatments yet. New inhibitor designs could have the potential to improve current drugs' efficacy, and so in this work, chemical intuition and bioisosteric replacement were used to computationally design two novel sEH inhibitors. These new candidates showed good pharmacokinetic properties and presented better docking scores compared to a known sEH inhibitor, t-TUCB, used in the treatment of pain in horses. Homology analysis revealed that Mus musculus may not be suitable organism for preclinical trials studies of these novel inhibitors.

中文翻译：

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两种新型可溶性环氧水解酶（sEH）抑制剂的计算设计

可溶性环氧化物水解酶（sEH）酶的抑制剂已显示出治疗神经性疼痛的巨大潜力。但是，目前的sEH抑制剂的理化性质较差，尚未被证明对人体治疗安全。新的抑制剂设计可能具有提高当前药物疗效的潜力，因此在这项工作中，化学直觉和生物等位取代被用于计算设计两种新型sEH抑制剂。与用于治疗马匹疼痛的已知sEH抑制剂t-TUCB相比，这些新候选药物显示出良好的药代动力学特性，并且具有更好的对接分数。同源性分析显示，小家鼠可能不适合用于这些新型抑制剂的临床前试验研究。