Biological and Medicinal Chemistry

Heterobifunctional Molecules Induce Dephosphorylation of Kinases - a Proof of Concept Study

Steve Staben Genentech, Inc.

Abstract

Previous work has shown that heterodimeric molecules, in some instances referred to as PROteolysis Targeting Chimeras, promote proximity of an E3-ligase to a target of interest to induce target ubiquitination. We hypothesize that many other PTMs, beyond ubiquitination, can be catalyzed in a similar matter. This work utilizes recruitment of PP1 (protein phosphatase 1) to induce de phosphorylation of target proteins (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.

Content

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Supplementary material

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2019 07 24 PP1 recruiter communication supp info