Development of a High Throughput Screening Galanin 3 Receptor Assay

高通量筛选甘丙肽 3 受体检测方法的开发

• 批准号: 7172042
• 负责人: Steven J Brown
• 金额: $ 23.24万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172042
• 关键词: NIH Roadmap Initiative tag; blood brain barrier; cell surface receptors; drug discovery /isolation; high throughput technology; neuropeptides; pharmacology; small molecule; technology /technique development

DESCRIPTION (provided by applicant): The major purpose of this Assay Development Proposal is to provide a key step in a fully integrated effort towards the goal of finding small molecule pharmacological tools for the Galanin 3 Receptor. The Scripps Research Institute (TSRI) is a center of excellence in chemistry and biology and its investigators have a strong record of success in identifying and characterizing small molecule pharmacological tools. The Scripps Molecular Libraries Screening Center (MLSC) is taking an active role supporting the NIH Roadmap's effort to identify useful molecular tools. To create excellent small molecule discovery opportunities for eventual submission to the MLSC Network through the X01 application mechanism, we would like to enhance critical basic receptor tools for a clinically important neuroscience target, and ready this system for high throughput biology. 1. Develop a GALR3 beta-lactamase reporter assay and counter screens for high throughput screening. 2. Format and validate the GALR3 antagonist assay for HTS 3. Define the pathway for evaluating HTS derived compound leads in vitro and in vivo Galanin is a neuropeptide with three GPCRs (GALR1-3) that mediates its effects in the brain and peripheral nervous system. GALR3 represents a novel target for antidepressant drug action and there is a great medical need for antidepressants with new mechanism of action. Potent, specific and bioavailable GALR3 antagonists are needed to further validate this target for the treatment of anxiety and depression. Compounds with the desired profile of high potency, selectivity and ability to cross the blood-brain barrier (BBB) will be evaluated in animal models of anxiety and depression. Proof of concept (POC) studies with Galanin receptor agonists and antagonists may ultimately lead to improved therapeutic modalities for several neurological diseases.

描述（由申请人提供）：本检测开发提案的主要目的是为寻找甘丙肽3受体的小分子药理学工具的目标提供一个全面整合的关键步骤。斯克里普斯研究所（TSRI）是一个卓越的化学和生物学中心，其研究人员在识别和表征小分子药理学工具方面取得了成功。斯克里普斯分子文库筛选中心（MLSC）正在积极支持NIH路线图的努力，以确定有用的分子工具。为了创造优秀的小分子发现机会，最终通过X01应用机制提交给MLSC网络，我们希望为临床重要的神经科学靶点增强关键的基础受体工具，并为高通量生物学系统做好准备。1. 开发GALR3 β -内酰胺酶报告试验和计数器筛选高通量筛选。2. 编制并验证GALR3拮抗剂HTS 3试验。甘丙肽是一种具有三个gpcr （GALR1-3）的神经肽，介导其在大脑和周围神经系统中的作用。GALR3是抗抑郁药物作用的新靶点，对具有新的作用机制的抗抑郁药物有很大的医学需求。需要有效的、特异性的和生物可利用的GALR3拮抗剂来进一步验证这一靶点治疗焦虑和抑郁的效果。具有高效、选择性和穿越血脑屏障（BBB）能力的化合物将在焦虑和抑郁动物模型中进行评估。丙氨酸受体激动剂和拮抗剂的概念验证（POC）研究可能最终导致改善几种神经系统疾病的治疗方式。