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ID: ALA4354839

Journal: J Med Chem

Title: Heterobifunctional Molecules Induce Dephosphorylation of Kinases-A Proof of Concept Study.

Authors: Yamazoe S, Tom J, Fu Y, Wu W, Zeng L, Sun C, Liu Q, Lin J, Lin K, Fairbrother WJ, Staben ST.

Abstract: Heterobifunctional molecules have proven powerful tools to induce ligase-dependent ubiquitination of target proteins. We describe here a chemical strategy for controlling a different post-translational modification (PTM): phosphorylation. Heterobifunctional molecules were designed to promote the proximity of a protein phosphatase (PP1) to protein targets. The synthesized molecules induced the PP1-dependent dephosphorylation of AKT and EGFR. To our knowledge, this work represents the first examples of small molecules recruiting non-native partners to induce removal of a PTM.

CiteXplore: 31874036

DOI: 10.1021/acs.jmedchem.9b01167