Highly Multiplexed Cell-Based GPCR Assay.

项目总结/摘要 我们的目标是商业化一个新的检测系统，检测和定量受体 下调/脱敏和受体再敏化，对于大量的 人类GPCR平行。这种小型化、多路复用和可扩展的系统使 不同的GPCR发现项目，它大大降低了每个目标的成本， 初级和二级药物筛选，从而缓解了 开发新的治疗分子。在拟议工程计划的第一期，我们会 在23种人脂质和核苷的阵列转染和测定自动化中验证 受体。在第二阶段，该集将扩展到包括完整的人类 内源性GPCR库。新系统将：（1）使化学和生物 在一个高度敏感的环境中，针对完整的人GPCR库筛选文库。 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）提供了一种有效的手段，使人类GPCR的不确定 功能，其中超过100目前存在，（4）提供一个新的和负担得起的 基础研究的工具。 !

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. !