Discovery of novel small molecule analgesics

新型小分子镇痛药的发现

• 批准号: 8715453
• 负责人: Roslyn Rivkah ISSEROFF
• 金额: $ 24.5万
• 依托单位: EPIGEN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8715453
• 关键词: Agonist; Analgesics; Area; Autoimmune Process; Behavioral; Biochemical; Biological Assay; Burning Pain; CYP2D6 gene; CYP3A4 gene; Cancer cell line; Cell Line; Chemistry; Cisplatin; Clinical; Coupled; Cytokine Suppression; Development; Diabetes Mellitus; Dose; Esthesia; Human; Hyperalgesia; Hypersensitivity; In Vitro; Inhibitory Concentration 50; Injury; Laboratory Research; Lead; Literature; Liver Microsomes; Measures; Mediating; Medical; Modeling; Mus; Nerve; Nociception; Pain; Peripheral nerve injury; Permeability; Persistent pain; Pharmaceutical Chemistry; Pharmaceutical Preparations; Prevention; Process; Production; Property; Receptor Activation; Relative (related person); Reporting; Research Support; Resolution; Sensory; Signal Transduction; Small Business Technology Transfer Research; Spinal; Stimulus; Structure-Activity Relationship; Symptoms; TLR4 gene; TNF gene; Tactile; Testing; Therapeutic; Therapeutic Agents; Therapeutic immunosuppression; Toll-like receptors; allodynia; base; cancer therapy; chemotherapy; cytokine; cytotoxic; design; disability; drug discovery; epigen; experience; in vivo; interest; macrophage; medical schools; meetings; mouse model; nerve injury; novel; painful neuropathy; pathogen; pharmacophore; pre-clinical; prevent; public health relevance; research study; response; safety testing; small molecule

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.

描述(申请人提供)：周围神经损伤可导致异常感觉，称为神经病理性疼痛。神经损伤可能是由各种侮辱引起的，从直率地切断或压迫神经，到化疗和自身免疫条件。症状通常包括持续的灼热疼痛和异常的感觉感觉，如超敏(非伤害性刺激引起的疼痛)和痛敏(对正常疼痛刺激的反应增加)，在临床可察觉的化疗迹象消失后持续疼痛构成治疗挑战，而免疫抑制治疗不能满足这一医学需要。因此，需要新的治疗方案，在缓解疼痛方面提供额外的好处。在这项提议中，Eigen Biosciences Inc.经验丰富的药物化学能力将使发现和开发具有合适的止痛药性质的新型小分子成为可能。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。加州大学圣迭戈分校将在疼痛模型中评估先导化合物。拟议的项目旨在开发治疗疼痛的小分子疗法。