AZ1 | USP25/28 inhibitor

AZ1 chemical structure

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AZ1 (2165322-94-9) is a selective dual inhibitor of the deubiquitinases USP25 and 28 (IC50’s = 620 nM and 700 nM respectively).1 It reduced c-Myc levels in HCT116, SW480, and HT29 colon cancer cell lines. AZ1 inhibited SARS-CoV-2 replication in Vero E6 cells.2  It caused DNA damage, promoted c-Myc degradation, and induced apoptosis in non-small cell lung cancer cells alone and in combination with cisplatin.3 Treatment of chronic lymphocytic leukemia cells with AZ1 suppressed Notch activation and reduced cell viability in combination with venetoclax.4 It reduced c-Myc expression in clear cell renal cell carcinoma leading to tumor growth suppression.5 AZ1 ameliorated Parkinson’s disease via USP25-dependent restoration of mitophagy.6

References/Citations:

  1. Wrigley et al. (2017), Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily; ACS Chem. Biol., 12 3113
  2. Kim et al. (2022), A proteome-scale map of the SARS-CoV-2-human contactome; Nat. Biotech., 41 140
  3. Song et al. (2024), Deubiquitinating enzyme USP28 inhibitor AZ1 alone and in combination with cisplatin for the treatment of non-small cell lung cancer; Apoptosis, 29 1793
  4. Ehrmann et al. (2025), NOTCH1 signaling is dysregulated by loss of the deubiquitinase USP28 with del(11q), uncovering USP28 inhibition as novel therapeutic target in CLL; Leukemia, 39 1892
  5. Ren et al. (2026), Targeting USP28 inhibits clear cell renal cell carcinoma growth; Cell Signal., 139 112344
  6. Xu et al. (2026), USP25 inhibition ameliorates Parkinson’s disease by restoring mitophagy; Proc. Natl. Acad. Sci. USA, 123 e2516471123
2165322-94-9, AZ1 supplier, AZ1 USP inhibitor, USP25 inhibitor, USP25/28 inhibitor, USP28 inhibitor

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AZ1 (2165322-94-9) is a selective dual inhibitor of the deubiquitinases USP25 and 28 (IC50’s = 620 nM and 700 nM respectively).1 It reduced c-Myc levels in HCT116, SW480, and HT29 colon cancer cell lines. AZ1 inhibited SARS-CoV-2 replication in Vero E6 cells.2  It caused DNA damage, promoted c-Myc degradation, and induced apoptosis in non-small cell lung cancer cells alone and in combination with cisplatin.3 Treatment of chronic lymphocytic leukemia cells with AZ1 suppressed Notch activation and reduced cell viability in combination with venetoclax.4 It reduced c-Myc expression in clear cell renal cell carcinoma leading to tumor growth suppression.5 AZ1 ameliorated Parkinson’s disease via USP25-dependent restoration of mitophagy.6

References/Citations:

  1. Wrigley et al. (2017), Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily; ACS Chem. Biol., 12 3113
  2. Kim et al. (2022), A proteome-scale map of the SARS-CoV-2-human contactome; Nat. Biotech., 41 140
  3. Song et al. (2024), Deubiquitinating enzyme USP28 inhibitor AZ1 alone and in combination with cisplatin for the treatment of non-small cell lung cancer; Apoptosis, 29 1793
  4. Ehrmann et al. (2025), NOTCH1 signaling is dysregulated by loss of the deubiquitinase USP28 with del(11q), uncovering USP28 inhibition as novel therapeutic target in CLL; Leukemia, 39 1892
  5. Ren et al. (2026), Targeting USP28 inhibits clear cell renal cell carcinoma growth; Cell Signal., 139 112344
  6. Xu et al. (2026), USP25 inhibition ameliorates Parkinson’s disease by restoring mitophagy; Proc. Natl. Acad. Sci. USA, 123 e2516471123