EN171 is a covalent ligand that covalently targets both C38 and C96 on 14-3-3 to enhance 14-3-3 interactions with ERα, YAP and TAZ, leading to impaired estrogen receptor and Hippo pathway transcriptional activity. EN171 can not only be used as a molecular glue to enhance native protein interactions but can also be used as a covalent 14-3-3 recruiter in heterobifunctional molecules to sequester nuclear neo-substrates such as BRD4 and BLC6 into the cytosol.
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