This review summarizes recent synthetic advances for glutarimide scaffolds enabling cereblon-mediated targeted protein degradation.
A systematic investigation of cyclic imide stereoisomers in small molecules, peptides, and proteins, examining their racemization, CRBN engagement, ternary complex formation in vitro, and resulting degradation outcomes in cells.
Ternary complex structural knowledge enabled elucidation of structure–degradation relationships that will assist the future design of cereblon modulators that avoid GSPT1 toxicity.
This Perspective assimilates developments in sulfonyl exchange chemical biology that have driven exciting advances in drug discovery and fundamental research over the last decade.
This schematic illustrates the multidimensional optimization strategies for BRD4-targeting PROTACs, encompassing the rational design of the ternary complex, diverse controllable activation systems, and targeted delivery approaches.