G protein-coupled receptors (GPCRs) have been exploited as primary targets for drug discovery, and GPCR dimerization offers opportunities for drug design and disease treatment. An important strategy for targeting putative GPCR dimers is the use of bivalent ligands, which are single molecules that contain two pharmacophores connected through a spacer. Here, we discuss the selection of pharmacophores, the optimal length and chemical composition of the spacer, and the choice of spacer attachment points to the pharmacophores. Furthermore, we review the most recent advances (from 2018 to the present) in the design, discovery and development of bivalent ligands. We aim to reveal the state-of-the-art design strategy for bivalent ligands and provide insights into future opportunities in this promising field of drug discovery.

G 蛋白偶联受体 (GPCR) 已被用作药物发现的主要目标，GPCR 二聚化为药物设计和疾病治疗提供了机会。靶向假定 GPCR 二聚体的一个重要策略是使用二价配体，它们是包含两个通过间隔连接的药效团的单分子。在这里，我们讨论了药效团的选择、间隔物的最佳长度和化学成分，以及药效团的间隔物附着点的选择。此外，我们回顾了二价配体的设计、发现和开发的最新进展（从 2018 年至今）。我们的目标是揭示二价配体的最先进设计策略，并提供对这个有前途的药物发现领域未来机会的见解。