CAS-010 (CAS-13312-010) is a potent and selective USP28 inhibitor with an IC50 of 2.2 nM against full-length USP28. CAS-010 acts as a ubiquitin-competitive inhibitor and shows higher selectivity over USP25 (IC50 = 51 nM) and other USP family members, disrupting the 53BP1-USP28 interaction and suppressing p53-dependent transcription of CDKN1A (p21), MDM2, and BAX. CAS-010 can be used for studying USP28-mediated DNA damage response and p53 signaling in cancer-related research [1].
In Vitro, CAS-010 (0.1-10 μM; 24 h) regulates the p53 transcriptional program, upregulates p21 and MDM2 expression, and promotes 53BP1-USP28 complex formation in U2OS cells[1]. CAS-010 (0.03-10 μM; 24 h) induces p53 target gene expression and enhances p53 transcriptional activity in HCT116 cells[1]. CAS-010 (dose-dependent; 5 d) inhibits the proliferation of multiple cancer cell lines, and its cellular activity profile strongly correlates with the USP28 knockout phenotype[1].
References:
[1]. Bratt AS, et al. Pharmacologic interrogation of USP28 cellular function in p53 signaling. Cell Chem Biol. 2025 Sep 18;32(9):1166-1182.e27.
In Vitro, CAS-010 (0.1-10 μM; 24 h) regulates the p53 transcriptional program, upregulates p21 and MDM2 expression, and promotes 53BP1-USP28 complex formation in U2OS cells[1]. CAS-010 (0.03-10 μM; 24 h) induces p53 target gene expression and enhances p53 transcriptional activity in HCT116 cells[1]. CAS-010 (dose-dependent; 5 d) inhibits the proliferation of multiple cancer cell lines, and its cellular activity profile strongly correlates with the USP28 knockout phenotype[1].
References:
[1]. Bratt AS, et al. Pharmacologic interrogation of USP28 cellular function in p53 signaling. Cell Chem Biol. 2025 Sep 18;32(9):1166-1182.e27.