Drug-Target Association Kinetics in Drug Discovery

The important role of ligand-receptor binding kinetics in drug design and discovery is increasingly recognized by the drug research community. Over the past decade, accumulating evidence has shown that optimizing the ligand's dissociation rate constant can lead to desirable duration of in vivo target occupancy and, hence, improved pharmacodynamic properties. However, the association rate constant as a pharmacological principle remains less investigated, whereas it can play an equally important role in the selection of drug candidates. This review provides a compilation and discussion of otherwise scarce and dispersed information on this topic, bringing to light the importance of drug -target association in kinetics-directed drug design and discovery.

配体 - 受体结合动力学在药物设计和发现中的重要作用日益受到药物研究界的认可。在过去的十年中，越来越多的证据表明，优化配体的解离速率常数能够使体内靶点占有率达到理想的持续时间，从而改善药效特性。然而，结合速率常数作为一种药理学原理，其研究相对较少，尽管它在候选药物的筛选中可能起着同样重要的作用。本综述对这一主题上原本稀缺且分散的信息进行了汇编和讨论，揭示了药物 - 靶点结合在动力学导向的药物设计和发现中的重要性。