Prioritizing adaptive probe performance over static specificity metrics Small-molecule probes, ligands, and inhibitors inevitably experience off-target interactionsparticularly in redox-active systems where enzymes such as TrxR, GR, and other oxidoreductases share overlapping catalytic motifs, cofactors, and substrate preferences
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1 Introduction Osteoarthritis (OA) is among the most prevalent degenerative joint diseases globally, affecting more than 500 million people worldwide and ranking as the leading cause of disability among adults aged 50 years and older ( Ferroptosis, first reported in 2012, is a novel form of cell death distinct from classical apoptosis, pyroptosis, and necrosis ( Due to the possible critical role of ferroptosis in OA, there has been a surge of interest in elucidating its molecular mechanisms and exploring potential therapeutic strategies
