Assessing the Cell Permeability of Bivalent Chemical Degraders Using the Chloroalkane Penetration Assay.

ABSTRACT: Bivalent chemical degraders provide a catalytic route to selectively degrade disease-associated proteins. By linking target-specific ligands with E3 ubiquitin ligase recruiting ligands, these compounds facilitate targeted protein ubiquitination and degradation by the proteasome. Due to the complexity of this multistep mechanism, the development of effective degrader molecules remains a difficult, lengthy, and unpredictable process. Since degraders are large heterobifunctional molecules, the efficacy of these compounds may be limited by poor cell permeability, and an efficient and reliable method to quantify the cell permeability of these compounds is lacking. Herein, we demonstrate that by the addition of a chloroalkane tag on the BRD4 specific degrader, MZ1, cell permeability can be quant

SUBMITTER: Foley CA 

PROVIDER: S-EPMC7010361 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature