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异常感觉，称为神经性疼痛。神经损伤可由多种损伤引起，包括通过切片或压迫直接损伤神经、化疗和自身免疫性疾病。症状通常包括持续的灼痛和异常的感觉，如异常痛觉（由非有害刺激引起的疼痛）和痛觉过敏（对正常疼痛刺激的反应增加）。在化疗的临床明显迹象消退后，持续的疼痛带来了治疗挑战，免疫抑制疗法不能满足这种医疗需求。因此，需要新的治疗方案，以提供额外的好处，以减轻疼痛。在这项提案中，Epigen Biosciences Inc.经验丰富的药物化学能力将能够发现和开发具有适合药物性质的新型小分子。化学发展将与加州大学戴维斯分校医学院的体外能力相结合，以测试这些化合物。铅化合物将在UCSD的疼痛模型中进行评估。该项目旨在开发治疗疼痛的小分子药物。

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.