作用于G蛋白偶联受体药物设计方法的新进展

Research progress in the design methods of drugs acting on G protein-coupled receptor

G蛋白偶联受体(G protein-coupled receptor,GPCR)作为一类重要的膜蛋白受体,一直以来都是新药开发中最重要的靶标之一。既往许多药物都是GPCR的调质分子。随着GPCR膜稳定性问题的解决、GPCR结构生物学的发展以及大量药物研究新技术的应用,GPCR新药开发不再局限于传统的高通量筛选等方法。基于受体蛋白结构(SBDD)和配体片段(FBDD)的药物设计方法迅速发展起来,最突出的应用是作用于β-肾上腺素受体和腺苷受体新型配体分子的筛选和鉴定研究。

As an important membrane protein receptor, G protein-coupled receptor （GPCR） was one of the most important targets in the development of new drugs. Previously, many drugs acting on GPCR were GPCR modulators. With the solution of membrane stability of GPCR, the development of GPCR structural biology and the application of a large number of new drug research methods, the development of new drugs was no longer just limited to traditional high-throughput screening methods. Both structure-based drug design （SBDD） and fragment-based drug discovery （FBDD） have developed rapidly in recent years. The most prominent applications were the screening and verification of novel ligands acting on the β-adrenergic receptor and the adenosine receptor.