Abstract:
The proximity-induced strategy artificially induces spatial proximity between a target protein and an effector protein, triggering post-translational modifications such as ubiquitination and phosphorylation, thereby realizing a pharmacological paradigm shift from "occupancy-driven" to "event-driven" modalities. Within this framework, kinase molecular glues have emerged as a novel class of therapeutic tools that enable the precise regulation of kinase functions by facilitating interactions between kinases and E3 ubiquitin ligases or other regulatory proteins. This review systematically summarizes recent advances in kinase molecular glues, encompassing three major directions: CRBN-based molecular glue degraders (MGDs), non-CRBN MGDs, and non-degrading molecular glues, with the aim of providing a reference for the research and development of molecular glues.