Highly Multiplexed Cell-Based GPCR Assay.

项目摘要/摘要 我们的目标是将一种新的检测和量化受体的检测系统商业化 下调/脱敏和受体重新增敏，对大量 人类的GPCR是平行的。这种小型化、多路复用和可扩展的系统使 多样化的GPCR发现项目，它显著降低了 一次和二次药物筛查，从而缓解了 开发新的治疗分子。在拟议项目的第一阶段，我们将 23种人脂和核苷基因芯片转染及自动化检测的验证 感受器。在阶段2中，集合将被扩展到包括完整的人类 内源性GPCR谱。新系统将：(1)使化学和生物 将根据完整的人类GPCR谱系进行高度筛选的文库 多种形式，(2)通过揭示以下选择性模式来改进药物开发 可以解决，以产生更精确的靶向，更有效的治疗 分子，(3)提供了一种有效的方法来使不确定的人的GPCRs去孤儿 功能，其中目前存在100多个功能，以及(4)提供一种新的、负担得起的 基础研究的工具。 好了！

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. !