A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development.

ABSTRACT: Bifunctional molecules such as targeted protein degraders induce proximity to promote gain-of-function pharmacology. These powerful approaches have gained broad traction across academia and the pharmaceutical industry, leading to an intensive focus on strategies that can accelerate their identification and optimization. We and others have previously used chemical proteomics to map degradable target space, and these datasets have been used to develop and train multiparameter models to extend degradability predictions across the proteome. In this study, we now turn our attention to develop generalizable chemistry strategies to accelerate the development of new bifunctional degraders. We implement lysine-targeted reversible-covalent chemistry to rationally tune the binding kinetics at the pro

SUBMITTER: Fan AT 

PROVIDER: S-EPMC11890178 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature