USP30-I-1

USP30-I-1 is a potent and selective cyanopyrrolidine-based covalent inhibitor of the mitochondrial deubiquitinase USP30, designed to enhance mitophagy by targeting the catalytic cysteine (Cys77) with high specificity at concentrations ≤1 μM. USP30-I-1 demonstrates dose-dependent inhibition with an IC50 of 94 nM in neuroblastoma cells, efficiently blocking USP30 activity with no significant toxicity reported in the tested models and no adverse effects on non-target proteins within the tested concentration range. USP30-I-1’s kinetic profile (kinact/KI = 0.18 μM⁻¹s⁻¹) highlights its effective covalent bond formation, while in vitro studies confirm its ability to disrupt ubiquitin-substrate interactions essential for mitophagy regulation.