An MLSCN for GPCRs Ion Channels, and Transporters(RMI)

用于 GPCR 离子通道和转运蛋白 (RMI) 的 MLSCN

• 批准号: 7408876
• 负责人: C DAVID WEAVER
• 金额: $ 29.23万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7408876
• 关键词: Archives; Area; Basic Science; Biological; Biological Assay; Biology; Calibration; Cells; Chemicals; Chemistry; Collaborations; Communication; Communities; Core Facility; Data; Data Analyses; Dedications; Drug Delivery Systems; G-Protein-Coupled Receptors; Generations; Individual; Industry; Ion Channel; Knowledge; Laboratories; Ligands; Maintenance; Methods; Molecular Bank; Operative Surgical Procedures; Organic Chemistry; Personal Satisfaction; Pharmacologic Substance; Physiological; Play; Property; Proteins; Protocols documentation; Publications; Reporting; Research; Research Personnel; Role; Screening procedure; Signal Pathway; Standards of Weights and Measures; Structure-Activity Relationship; System; Technology; Therapeutic Agents; Translating; Translational Research; United States National Institutes of Health; Universities; Work; base; data management; high throughput screening; improved; instrument; instrumentation; interest; new technology; novel; small molecule; tool

DESCRIPTION (provided by applicant): G-protein coupled receptors (GPCRs), ion channels, and transporters are areas of intense basic research and are proven drug targets. However, there remains a need for new tools to develop a better understanding of the roles of these proteins in biological systems and to pave the way for discovery of therapeutic agents. Although ligand discovery has been performed on these proteins in pharmaceutical companies, their retail product interests often preclude, or greatly delay, the publication of research findings or consider only one of the many possible modes of target/small molecule interaction. Despite intense interest of multiple academic and industry labs, small molecules ligands do not exist for the vast majority of GPCRs, ion channels, and transporters. The research community, supported by the Molecular Libraries and Screening Centers Network (MLSCN) initiative, has an excellent opportunity to develop novel tools to aid in understanding these proteins. Thus, we propose to develop a MLSCN screening center focused on the generation of chemical tools for the study of G-protein coupled receptors, ion channels, and transporters. We will perform cell-based functional HTS for these proteins using industry-standard instrumentation and screening methods. We will further enhance our ability to rapidly discover and characterize novel tools for these targets and the signaling pathways/physiological systems of which they are a part by using new technologies that will allow more physiologically-relevant interrogation of interactions between these proteins and their partners. We will develop the expertise, technologies, and methods to understand and improve the properties of small molecules discovered through HTS to produce tools to support basic and translational research. Vanderbilt University is well suited to support an MLSCN center due to its combination of basic and industrial research expertise in the proposed target areas, its dedication to translational and chemical biology, and its tradition of excellence in the establishing and maintaining highly-collaborative laboratories and core facilities.

描述（由申请人提供）：G蛋白偶联受体（GPCR），离子通道和转运蛋白是强烈的基础研究领域，并且已被证明是药物靶标。但是，仍然需要新工具来更好地理解这些蛋白质在生物系统中的作用，并为发现治疗剂铺平道路。尽管在制药公司的这些蛋白质上进行了配体发现，但其零售产品的兴趣通常排除或极大地延迟了研究发现的发布，或者仅考虑了靶标/小分子相互作用的许多可能模式之一。尽管多个学术和行业实验室的强烈兴趣，但绝大多数GPCR，离子渠道和转运蛋白的小分子并不存在。在分子图书馆和筛选中心网络（MLSCN）倡议的支持下，研究界有一个很好的机会来开发新颖的工具来帮助理解这些蛋白质。因此，我们建议开发一个MLSCN筛选中心，该筛查中心重点是生成用于研究G蛋白偶联受体，离子通道和转运蛋白的化学工具。我们将使用行业标准的仪器和筛选方法对这些蛋白质进行基于细胞的功能HTS。我们将进一步增强我们快速发现和表征这些目标的新工具以及信号通路/生理系统的能力，它们通过使用新技术，这些技术将允许对这些蛋白质及其伴侣之间的相互作用进行更多与生理相关的询问。我们将开发专业知识，技术和方法，以了解和改善通过HTS发现的小分子的特性，以生产支持基本和转化研究的工具。范德比尔特大学（Vanderbilt University）非常适合支持MLSCN中心，因为它在拟议的目标领域的基本和工业研究专业知识，对翻译和化学生物学的奉献精神以及其在建立和维护高度合并的实验室和核心设施方面的卓越传统。