I-Corps training for 1R41NS086244-A01 Discovery of novel small molecule analgesics

描述（由申请人提供）：周围神经损伤可导致称为神经性疼痛的异常感觉。神经损伤可由多种损伤引起，从通过切片或压迫对神经的直接损伤，到化疗和自身免疫性疾病。症状通常包括持续的烧灼痛和异常感觉，例如异常性疼痛（由于非伤害性刺激引起的疼痛）和痛觉过敏（对正常疼痛刺激的反应增加）。在临床上可感知的化疗体征消退后的持续疼痛构成了治疗挑战，免疫抑制疗法不能满足这种医疗需求。因此，需要在缓解疼痛方面提供额外益处的新型治疗选择。在本提案中，Epigen Biosciences Inc.将能够发现和开发具有合适的止痛药样特性的新型小分子。化学开发将与加州大学戴维斯分校医学院的体外能力相结合，以测试化合物。铅化合物将在UCSD的疼痛模型中进行评估。该拟议项目旨在开发治疗疼痛的小分子疗法。

DESCRIPTION (provided by applicant): Peripheral nerve injury can lead to anomalous sensations referred to as neuropathic pain. Nerve injury may result from a variety of insults ranging from frank injury to the nerve though sectioning or compression, to chemotherapeutics and autoimmune conditions. Symptoms often include continuous burning pain and abnormal sensory sensations such as allodynia (pain as a result of non-noxious stimuli) and hyperalgesia (an increased response to a normally painful stimulus) Persistent pain after resolution of clinically appreciable signs of chemotherapy poses a therapeutic challenge and immunosuppressive therapies do not meet this medical need. Accordingly, novel treatment options that afford additional benefit in relief of pain are needed. In this proposal, the experienced medicinal chemistry capabilities of Epigen Biosciences Inc. will enable the discovery and development of novel small molecules with suitable drug like properties for pain. The chemistry development will be coupled with the in vitro capabilities of UC Davis Medical School to test the compounds. Lead compounds will be assessed in pain models at UCSD. The proposed project is designed to develop small molecule therapeutics for pain.