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Inactivator and inhibitors of cysteine proteases. (A) Structure of K777 and its mechanism of covalent inactivation of cysteine proteases. (B) 1,2,4-trioxolane inhibitor PG4b undergoes Fe(II)-catalyzed fragmentation to elaborate aldehyde PG3b, a potent inhibitor of falcipain, and a radical byproduct. (C) γ-lactol inhibitor MN3 is a masked aldehyde of SJA0617. It exhibits higher transcorneal permeability and releases the free aldehyde to inhibit μ-calpain.
