Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential
Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential
复制标题
G 蛋白偶联受体 (GPCR) 的偏向配体：结构-功能选择性关系 (SFSR) 和治疗潜力。
DOI：
10.1021/acs.jmedchem.8b00435
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发表时间：
2018-11-22
影响因子：
7.3
通讯作者：
Cheng, Jianjun
中科院分区：
文献类型：
--
作者：
Tan, Liang;Yan, Wenzhong;Cheng, Jianjun
G蛋白偶联受体（GPCR）通过G蛋白依赖性和G蛋白非依赖性途径传递信号，β-抑制蛋白募集是后者中最受认可的一种。预期对任一途径具有选择性的偏置配体以更精确的方式调节GPCR的生物学功能，因此提供具有上级功效和/或降低的副作用的新药物分子。在过去的十年中，已经发现并开发了许多GPCR的偏向性配体，例如μ阿片受体、1型血管紧张素II受体、多巴胺D-2受体等。在这个角度来看，在这一领域的最新进展进行了审查，讨论GPCR偏向配体的结构-功能选择性关系（SFSRs）和这些分子的治疗潜力。进一步了解与每个信号通路相关的生物学功能和偏向信号的结构基础将有助于该领域未来的药物设计。
G protein-coupled receptors (GPCRs) signal through both G-protein-dependent and G-protein-independent pathways, and beta-arrestin recruitment is the most recognized one of the latter. Biased ligands selective for either pathway are expected to regulate biological functions of GPCRs in a more precise way, therefore providing new drug molecules with superior efficacy and/or reduced side effects. During the past decade, biased ligands have been discovered and developed for many GPCRs, such as the mu opioid receptor, the angiotensin II receptor type 1, the dopamine D-2 receptor, and many others. In this Perspective, recent advances in this field are reviewed by discussing the structure-functional selectivity relationships (SFSRs) of GPCR biased ligands and the therapeutic potential of these molecules. Further understanding of the biological functions associated with each signaling pathway and structural basis for biased signaling will facilitate future drug design in this field.