Proximity-inducing modalities: the past, present, and future
†a
Wenzhi
Tian,
†a
Zachary C.
Severance,
†a
Santosh K.
Chaudhary,
†a
Viktoriya
Anokhina,
†a
Basudeb
Mondal,
†a
Rajaiah
Pergu,
†a
Prashant
Singh,
†a
Uttam
Dhawa,
†a
Santanu
Singha
a
and
Amit
Choudhary
*abc
Abstract
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.
- This article is part of the themed collection: Modalities of induced proximity pharmacology: Degraders and Beyond themed collection
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