EN171, a covalent ligand, selectively binds to C38 and C96 on 14-3-3, intensifying 14-3-3s interactions with ERalpha, YAP, and TAZ. This action impairs both estrogen receptor and Hippo pathway transcriptional activities. Beyond serving as a molecular glue to augment native protein interactions, EN171 also functions as a covalent recruiter for 14-3-3 in heterobifunctional molecules. This facilitates the sequestration of nuclear neo-substrates, such as BRD4 and BLC6, into the cytosol.
