Illuminating the Druggable GPCR-ome

阐明可药物化的 GPCR-ome

• 批准号: 10249123
• 负责人: Bryan L. Roth
• 金额: $ 224.1万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249123
• 关键词: Animals; Area; Arrestins; Award; Biological Process; Biology; Biomedical Research; Cell Line; Chemicals; Chemistry; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communities; Databases; Development; Docking; Drug Targeting; Engineering; Epinephrine; Funding; G-Protein-Coupled Receptors; G-substrate; Genetic; Genetically Engineered Mouse; Goals; Heart Rate; Human; Human Genome; Individual; Informatics; Infrastructure; Learning; Light; Lipids; Memory; Modeling; Mus; Orphan; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Physiology; Plasmids; Protein Family; Reagent; Reporter; Reporter Genes; Research; Research Personnel; Resource Sharing; Resources; Respiration; Science; Signal Pathway; Signal Transduction; Specific qualifier value; Structure; Synthesis Chemistry; Technology; Testing; Therapeutic; Tissues; Transducers; Viral; Vision; Yeasts; base; cell type; chemical genetics; chemical synthesis; chemokine; computer infrastructure; computerized tools; data resource; data sharing; designer receptors exclusively activated by designer drugs; druggable target; experimental study; genetic approach; human disease; in vivo Model; large datasets; medical schools; new technology; novel; novel therapeutics; optogenetics; programs; public health relevance; screening; targeted treatment; tool

Project Summary G-protein coupled receptors (GPCRs) represent the single largest class of druggable targets in the human genome. Of the 390 or so druggable and non-olfactory human GPCRs there exist many which are orphan and/or understudied; we refer to these as “oGPCRs”. Here we will illuminate the pharmacology, signaling pathways, chemical biology, distribution and function of the 143 oGPCRs listed in the RFA. This project seeks to discover and develop specific, community accessible tools— chemical probe molecules and engineered animals—that enable investigators to interrogate the biological functions of oGPCRs. Given the central importance of GPCRs for all areas of biomedical research, illuminating the pharmacology, function, signaling and chemical biology of these oGPCRs will have far-reaching impact for both therapeutics and basic biomedical science.

项目摘要 G蛋白偶联受体（GPCR）代表了该靶标的最大的一类可药物靶标 人基因组。在390个左右的可吸毒和非野性人GPCR中，有许多 是孤儿和/或理解的；我们将其称为“ OGPCR”。在这里，我们将照亮 143 OGPCR的药理学，信号通路，化学生物学，分布和功能 在RFA中列出。该项目旨在发现和开发特定的，社区可访问的工具 - 化学探针分子和工程动物 - 使研究人员能够询问 OGPCR的生物学功能。鉴于GPCR对于所有生物医学领域的核心重要性 研究，阐明这些OGPCR的药理学，功能，信号和化学生物学 对治疗学和基本生物医学科学都有深远的影响。