ArticleJournal of the American Chemical Society2026
Harnessing FBXO31 with Terminal Amide-Functionalized Molecules for Targeted Protein Degradation.
Article in Journal of the American Chemical Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Targeted protein degradation (TPD) is a powerful strategy for controlling protein abundance. Here, we establish FBXO31 as a TPD-competent E3 ligase by exploiting its recognition of C-terminal amide-bearing degrons. Using an amidated Ala-Phe motif as a chemical recruiter, multiple small-molecule binders can be transformed into FBXO31-dependent degraders that induce the rapid and potent degradation of FKBP12, multiple kinases, and BET proteins BRD2, BRD3, and BRD4. Mechanistic studies confirm FBXO31-mediated ternary complex formation and identify key residues in FBXO31 required for recruiter engagement and target degradation.
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