Development of an Oral Analgesic for Neuropathic Pain

开发一种治疗神经性疼痛的口服镇痛药

• 批准号: 9461249
• 负责人: Alan R Buckpitt
• 金额: $ 12.52万
• 依托单位: EICOSIS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9461249
• 关键词: Absence of pain sensation; Adverse effects; Aging; Analgesics; Arachidonic Acids; Biological; Biological Assay; Blood; Canis familiaris; Cardiovascular system; Chemicals; Chemistry; Clinical Research; Clinical Trials; Collaborations; Consultations; Contractor; Cytochromes; Data; Development; Development Plans; Diabetes Mellitus; Diabetic Neuropathies; Dose; Dose-Limiting; Drug Kinetics; Economic Burden; Emotional; Enzymes; Epoxide hydrolase; Fatty Acids; Generations; Goals; Health; Human; Individual; Instruction; Laboratories; Lead; Legal patent; Lipids; Macaca fascicularis; Mediating; Mediator of activation protein; Modeling; Nerve; Nociception; Oral; Pain; Pain management; Peripheral Nervous System Diseases; Pharmacologic Substance; Phase; Phase I Clinical Trials; Polymorph; Population; Preparation; Property; Rattus; Rodent; Safety; Signal Transduction; Small Business Innovation Research Grant; Societies; Solubility; Technology; Therapeutic Agents; Toxic effect; Toxicokinetics; Toxicology; Work; base; chronic pain; clinical development; diabetic; diabetic patient; efficacy trial; follow-up; gastrointestinal; good laboratory practice; in vivo; inhibitor/antagonist; man; novel; novel therapeutics; painful neuropathy; physical property; preclinical development; preclinical efficacy; preclinical study; programs; relating to nervous system; safety testing; scale up; screening; small molecule inhibitor; small molecule libraries; type I diabetic; web site

Chronic pain is a debilitating health condition that is currently insufficiently treated by available therapies. There is a growing need to develop alternatives to treat chronic pain and specifically diabetic neuropathy as diabetes is increasing worldwide and painful neuropathy occurs in 50% of diabetic patients. Recently, the importance of lipids as signaling mediators and their functional significance in nociception has been elucidated. Epoxy-fatty acid metabolites generated by cytochrome P450s mediate analgesia, and we have synthesized small molecule inhibitors of their metabolizing enzyme, the soluble epoxide hydrolase (sEH), to elevate their levels in vivo. With this proposal, we aim to develop a novel and safe oral inhibitor of sEH for the treatment of peripheral neuropathy in diabetic patients. Preclinical studies with our candidate, EC5026, demonstrate efficacy that exceeds current therapies for diabetic neuropathy. Based on efficacy, good PK/ADME properties and stability, EicOsis has selected EC5026 to enter further development stages. EicOsis will work with Blueprint Development Teams to create a development plan and initiate studies to test the safety of EC5026 in Phase 1 clinical trials.

慢性疼痛是一种使人衰弱的健康状况，目前可用的治疗方法对其治疗不足。有