The intriguing role of USP30 inhibitors as deubiquitinating enzymes from the patent literature since 2013.

: Strategies towards mitophagy activation utilizing small-molecule inhibitors of USP30 have emerged as alternative pathways for the potential treatment of many human diseases. Research efforts have led to identifying good potent and selective small-molecule USP30 inhibitors. Most small-molecule USP30 inhibitors share a common N-cyano motif that binds covalently to the target. Non-covalently binding inhibitors have recently been disclosed as well. Lead compounds exhibit satisfactory inhibitory activities and are currently in preclinical development. Regrettably, complete pharmacological characterization and in vivo evaluation to validate and prove the therapeutic potential is lacking. Target validation could pave the way for discovering and developing USP30 inhibitors that could ultimately lead to marketed drugs.