Proximity-inducing modalities: the past, present, and future

Living systems use proximity to regulate biochemical processes. Inspired by this phenomenon, bifunctional modalities that induce proximity have been developed to redirect cellular processes. An emerging example of this class is molecules that induce ubiquitin-dependent proteasomal degradation of a protein of interest, and their initial development sparked a flurry of discovery for other bifunctional modalities. Recent advances in this area include modalities that can change protein phosphorylation, glycosylation, and acetylation states, modulate gene expression, and recruit components of the immune system. In this review, we highlight bifunctional modalities that perform functions other than degradation and have great potential to revolutionize disease treatment, while also serving as important tools in basic research to explore new aspects of biology.

Automated summary

Living systems regulate biochemical processes through proximity. Inspired by this, bifunctional modalities have been developed to redirect cellular processes. An emerging example is molecules that induce ubiquitin-dependent proteasomal degradation of a protein of interest, sparking discovery for other bifunctional modalities. Recent advances include modalities that can change protein phosphorylation, glycosylation, and acetylation states, modulate gene expression, and recruit components of the immune system. This review highlights non-degradation bifunctional modalities with potential to revolutionize disease treatment and explore new aspects of biology in basic research.