Proximity-Based Modalities for Biology and Medicine.

Molecular proximity orchestrates biological function, and blocking existing proximities is an established therapeutic strategy. By contrast, strengthening or creating neoproximity with chemistry enables modulation of biological processes with high selectivity and has the potential to substantially expand the target space. A plethora of proximity-based modalities to target proteins via diverse approaches have recently emerged, opening opportunities for biopharmaceutical innovation. This Outlook outlines the diverse mechanisms and molecules based on induced proximity, including protein degraders, blockers, and stabilizers, inducers of protein post-translational modifications, and agents for cell therapy, and discusses opportunities and challenges that the field must address to mature and unlock translation in biology and medicine.