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Noncovalent and covalent fragment-based approaches for hit finding and ligand development for E3 ligases. (A) Initial hit compound to the final clinical compound, ASTX660.87–89 (B–F) Examples of specific residue-selective covalent warheads: (B) cysteine,150 (D) lysine,151 and (F) methionine;152 and (C,E,G) the reaction mechanisms.
