2. Signaling Pathways
  3. Cell Cycle/DNA Damage
  4. Deubiquitinase
  5. USP30 Isoform

USP30

Deubiquitinase USP30 is a mitochondria-localized deubiquitinase positioned on the outer mitochondrial membrane, where it removes ubiquitin from mitochondrial substrates and functions as a key negative regulator of mitochondrial quality control pathways[1][2]. Mechanistically, USP30 antagonizes the PINK1-Parkin ubiquitination cascade by reversing Parkin-mediated ubiquitination of outer mitochondrial membrane proteins, thereby limiting mitophagy initiation and progression[1][3][4]. Through this activity, USP30 establishes a regulatory threshold for ubiquitin signaling on damaged mitochondria and influences the accumulation of mitophagy-associated ubiquitin modifications[3][5]. In disease-relevant models, genetic depletion or inhibition of USP30 enhances mitochondrial clearance, restores mitophagy defects associated with impaired PINK1 or Parkin function, and improves mitochondrial integrity in experimental systems linked to Parkinson’s disease[1][6]. Beyond neurodegeneration, USP30-dependent regulation of mitophagy has also been implicated in cellular stress responses, mitochondrial dysfunction, and age-associated pathological processes[7]. Compared with other deubiquitinases involved in mitochondrial quality control, USP30 is distinguished by its localization to the outer mitochondrial membrane and its direct antagonism of the PINK1-Parkin pathway, making it a prominent target for mechanistic studies of mitophagy regulation[2][8]. For experimental applications, highly selective small-molecule USP30 inhibitors, including N-cyano pyrrolidine-based compounds, increase ubiquitination of mitochondrial substrates and serve as useful tools for investigating mitophagy signaling and mitochondrial homeostasis[3][5].

USP30 Related Products (5):

Cat. No. Product Name Effect Purity
  • HY-141659
    CMPD-39
    		Inhibitor 99.74%
    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.
  • HY-P10416
    Q14
    		Inhibitor 98.51%
    Q14 is a polypeptide derived from the USP30 (ubiquitin specific peptidase 30) transmembrane (TM) domain with the ability to inhibit the deubiquitination activity of USP30 (IC50=57.2 nM). Q14 reduces USP30 activity by inhibiting the interaction between the USP30 transmembrane domain and its catalytic domain. Q14 peptide contains the LC3 interaction region (LIR) motif, which enables it to bind to the LC3 and accelerate the formation of autophagosomes, thereby promoting mitophagy. Q14 can be used in the study of neurodegenerative diseases as well as mitochondrial quality control and cell metabolism.
  • HY-182553
    USP30-IN-2
    		Inhibitor
    USP30-IN-2, a fused pyrroline, is an USP30 inhibitor with an IC50 <0.1 μM. USP30-IN-2 is expected to promote mitophagy and restore mitochondrial health. USP30-IN-2 can be used for research on Parkinson's disease.
  • HY-182636
    MT16-001
    		Inhibitor
    MT16-001 is a cell-permeable UCHL1 inhibitor with an IC50 value of 580 nM. MT16-001 also exhibits considerable inhibitory activity against USP30, and shows selectivity for other UCH family deubiquitinases (DUBs) as well as the broader proteome. MT16-001 binds covalently to the cysteine residue at the active site of UCHL1, and forms covalent interactions with ALDH2, ALDH9A1 and GATD3A in intact cells. Meanwhile, as a cytotoxic agent, it displays a steep dose-response curve in human embryonic kidney cells. MT16-001 can be used for research on various cancers, liver fibrosis and pulmonary fibrosis.
  • HY-175826
    USP30-IN-20
    		Inhibitor
    USP30-IN-20 is an orally active USP30 inhibitor (Kd = 1.61 μM, IC50 = 12.8 μM). USP30-IN-20 induces ferroptosis by promoting ubiquitination-mediated degradation of GPX4. USP30-IN-20 inhibits the proliferation, migration, invasion, and stemness of prostate cancer cells. USP30-IN-20 induces G0/G1 cell cycle arrest and ROS levels in prostate cancer cells. USP30-IN-20 exhibits significant anti-tumor efficacy in PC3 cell subcutaneous xenografts in mice. USP30-IN-20 can be used for the study of advanced prostate cancer.