CMPD-39

CMPD-39 is a selective non-covalent inhibitor of the ubiquitin-specific protease USP30 (IC₅₀=~20 nM), with high selectivity over other DUB family members (1-100 μM). CMPD-39 inhibits the deubiquitinating activity of USP30, enhances the ubiquitination of mitochondrial proteins TOMM20 and SYNJ2BP; thus, CMPD-39 promotes phosphoubuitin accumulation, thereby accelerating mitochondrial autophagy (mitophagy) and peroxisomal autophagy (pexophagy). CMPD-39 significantly restores impaired mitochondrial function in dopaminergic neurons derived from Parkinson's disease patients^[1][2]. In Vitro:CMPD-39 (200 nM; 1-4 h) significantly enhances the ubiquitination levels of TOMM20 and SYNJ2BP in RPE1-YFP-PRKN and SHSY5Y cells, and dependents on USP30 expression^[2].
CMPD-39 (1 μM; 96 h) enhances basal mitophagy in SHSY5Y-mitoQC cells and significantly increases the number and area of ??mitophagosomes^[2].
CMPD-39 (200 nM-1 μM; 96 h) significantly enhances peroxisomal autophagy in U2OS-Keima-SKL cells and increases the number and area of ??peroxisomes^[2].