靶向G蛋白偶联受体高通量药物筛选技术研究进展

摘要

G蛋白偶联受体(GPCR)是临床广泛应用药物的主要靶点之一.靶向GPCR的高通量药物筛选新技术不断涌现,为发现高效、高选择性、低毒的药物提供可能,并使选择合理的GPCR药物筛选策略显得尤为重要.本文综述了靶向GPCR药物高通量筛选相关技术及策略的研究进展,主要包括基于GPCR受体配体结合、第二信使、β-arrestin、调控元件报告基因、内化、聚合体及变构调节剂等方面的高通量药物筛选技术,以及相关技术的代表性商品化产品以供参考.%G protein-coupled receptors (GPCRs) are important drug targets, which have been widely used in clinical practice. New assay techniques for high-throughput screening of drugs targeting GPCRs are emerging in large numbers nowadays, providing the possibility to discover the more efficient, higher selective, lower toxic GPCR drugs. The techniques make the rational design and implementation for GPCR drug screening particularly important. In this paper, we reviewed the progress of techniques and strategies for high-throughput screening of drugs targeting GPCRs, mainly including the strategies on receptor-ligand binding, second messenger detection, (3-arrestin, reporter gene, internalization, oligomerizations and allosteric modulators. We also summarized some of the representative commercial techniques for reference.