PROTAC Compatibilities, Degrading Cell-Surface Receptors, and the Sticky Problem of Finding a Molecular Glue.

PROteolysis TArgeting Chimeras (PROTACs) are emerging as critical tools in biomedicinal chemistry and drug design, but they have limitations. These limitations include a lack of guiding principles when selecting suitable E3 ligases to induce ubiquitinylation, and problems degrading cell-surface receptors. This Highlight outlines some recent advances that circumvent some of these limitations, and new alternative methods to induce selective protein degradation.