Highly Multiplexed Cell-Based GPCR Assay.

高度多重的基于细胞的 GPCR 测定。

基本信息

批准号：
10077587
负责人：
G. Reid Asbury
金额：
$ 42.53万
依托单位：
SPECTRAGENETICS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10077587
关键词：
Address Agonist Archives Automation Basic Science Biological Biological Assay Cell Line Cells Chemicals Cloning Vectors Computer software DNA Development Disease Drug Screening Feedback G-Protein-Coupled Receptors Goals Human Lead Libraries Ligands Lipids Mammalian Cell Neurologic Nucleosides Output Pattern Peptide Receptor Phase Printing Psyche structure Signal Transduction Site Spottings Surface System Testing Therapeutic Transfection assay development base chemokine receptor cost desensitization drug development drug discovery expression vector graphical user interface improved miniaturize novel therapeutics peptide B receptor receptor downregulation response screening tool user-friendly vector

Address Agonist Archives Automation Basic Science Biological Biological Assay Cell Line Cells Chemicals Cloning Vectors Computer software DNA Development Disease Drug Screening Feedback G-Protein-Coupled Receptors Goals Human Lead Libraries Ligands Lipids Mammalian Cell Neurologic Nucleosides Output Pattern Peptide Receptor Phase Printing Psyche structure Signal Transduction Site Spottings Surface System Testing Therapeutic Transfection assay development base chemokine receptor cost desensitization drug development drug discovery expression vector graphical user interface improved miniaturize novel therapeutics peptide B receptor receptor downregulation response screening tool user-friendly vector

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项目摘要

Project Summary/Abstract Our goal is to commercialize a new assay system that detects and quantifies receptor downregulation/desensitization, and receptor resensitization, for large numbers of human GPCRs in parallel. This miniaturized, multiplexed and scalable system enables diverse GPCR discovery projects, and it dramatically lowers the cost-per-target in primary and secondary drug screens, thereby relieving major bottlenecks in the development of new therapeutic molecules. In phase 1 of the proposed project, we will validate in array transfection and assay automation for 23 human lipid and nucleoside receptors. In phase 2 the set will be extended to include the complete human endogenous GPCR repertoire. The new system will: (1) enable chemical and biologic libraries to be screened against the complete human GPCR repertoire in a highly multiplexed format, (2) improve drug development by revealing selectivity patterns that can be addressed to produce more precisely targeted, and more effective, therapeutic molecules, (3) provide an efficient means to deorphanize human GPCRs of uncertain function, of which more than 100 presently exist, and (4) provide a new and affordable tool for basic research. !

项目摘要/摘要我们的目标是商业化检测和量化受体的新测定系统大量的下调/脱敏和受体复敏人类GPCR并联。这个微型，多路复用和可扩展的系统启用多样化的GPCR发现项目，它大大降低了每目标的成本初级和次要药物筛查，从而减轻了主要瓶颈开发新的治疗分子。在拟议项目的第1阶段中，我们将验证23人脂质和核苷的阵列转染和测定自动化受体。在第2阶段中，该集将扩展到包括完整的人内源性GPCR曲目。新系统将：（1）启用化学和生物学在高度的人类GPCR曲目上筛选的库多路复用格式，（2）通过揭示选择性模式来改善药物开发可以解决以产生更精确的目标，更有效，治疗性分子，（3）提供了一种有效的手段，以脱字形的人GPCR不确定的人GPCR 功能，目前有100多个功能，（4）提供了一个新的且负担得起的基础研究工具。呢