Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany.
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany.
Drug Discov Today. 2019 Apr;24(4):1031-1037. doi: 10.1016/j.drudis.2019.02.010. Epub 2019 Mar 1.
G-protein-coupled receptors (GPCRs) represent important drug targets with complex pharmacological characteristics. Biased signaling represents one important dimension, describing ligand-dependent shifts of naturally imprinted signaling profiles. Because biased GPCR modulators provide potential therapeutic benefits including higher efficiencies and reduced adverse effects, the identification of such ligands as drug candidates is highly desirable. This review aims to provide an overview of the challenges and strategies in the discovery of biased ligands. We show different approaches for biased ligand discovery in the example of G-protein-biased opioid analgesics and discuss possibilities to design biased ligands by targeting extracellular receptor regions.
G 蛋白偶联受体 (GPCRs) 是具有复杂药理学特征的重要药物靶点。偏向信号代表一个重要的维度，描述了天然印迹的信号谱的配体依赖性变化。由于偏向 GPCR 调节剂提供了潜在的治疗益处，包括更高的效率和减少不良反应，因此将此类配体作为候选药物进行鉴定是非常可取的。本综述旨在概述在发现偏向配体方面的挑战和策略。我们以 G 蛋白偏向性阿片类镇痛药为例，展示了偏向配体发现的不同方法，并讨论了通过靶向细胞外受体区域设计偏向配体的可能性。
