Development of a Soluble Epoxide Hydrolase Inhibitor to Spare or Replace Opioid Analgesics

摘要/摘要 EicOsis正在开发一种一流的止痛药，对神经性疼痛有效，将 更换和剂量备用阿片类药物，从而预防阿片类药物使用障碍(OUD)。的目标是 小分子抑制剂EC5026是可溶性环氧化物水解酶，是一种主要的调节酶 这调节了内源性生物活性脂质的活性。EC5026的开发是 目前正在进行中，正在向IND提交文件，并准备在 治疗人类的慢性疼痛。在这份提案中，我们概述了旨在实现以下步骤的目标 EC5026的临床人体临床试验以及其他临床前研究，以扩大 对在人类中出现的最常见的慢性疼痛情况的模型的有效性 用阿片类药物治疗。此外，我们提出了详细的药代动力学、代谢和 将为高级临床试验提供所需信息的分布研究 在人类身上测试疗效。我们还建议优化配方以满足这些需求。 所有这些个人目标的结构都是为了满足两年的里程碑(UG3)并继续到 随着这些里程碑的实现，下一步计划的开发步骤(UH3)。EicOsis正在开会 当前的发展目标和EC5026处于有利地位，可以满足减少 阿片类药物的使用，因为即使给出了用多模式治疗疼痛的最新策略 治疗方法、药物是治疗疼痛的基础。EC5026代表着一款 类止痛药，既不是阿片类药物，也不是非甾体抗炎药，但能有效缓解慢性疼痛 神经性疼痛。

Summary/Abstract EicOsis is developing a first-in-class analgesic with efficacy against neuropathic pain that will replace and dose spare opioids and thus prevent opioid use disorders (OUDs). The target of the small molecule inhibitor EC5026 is the soluble epoxide hydrolase, a master regulatory enzyme that modulates the activity of endogenous bioactive lipids. The development of EC5026 is currently in progress and progressing to an IND filing and is poised to have a high impact in treating chronic pain in humans. In this proposal we outline aims to reach the next steps in clinical human clinical trials with EC5026 as well as additional preclinical studies to expand the efficacy into models of chronic pain conditions presenting in humans which are most frequently treated with opioids. Additionally, we propose detailed pharmacokinetic, metabolism and distribution studies that will provide the required information for advanced clinical trials examining efficacy in humans. We also propose to optimize a formulation to meet these needs. All of these individual aims are structured to meet 2 year milestones (UG3) and continue to the next planned steps in development (UH3) as these milestones are met. EicOsis is meeting current development goals and EC5026 is well positioned to meet the urgent need of reducing opioid use because even given the updated strategy to treating pain with multimodal approaches, pharmaceuticals are the foundation of treating pain. EC5026 represents a first-in- class analgesic that is not an opioid nor a NSAID but offers effective pain relief for chronic neuropathic pain.