SJB2-043

• CAT Number: I004390
• CAS Number: 63388-44-3
• Molecular Formula: C17H9NO3
• Molecular Weight: 275.26
• Purity: ≥95%
• Synonyms: 2-phenylbenzo[f][1,3]benzoxazole-4,9-dione
• Target: Deubiquitinase
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 0.544 uM (USP1) [1]

SJB2-043 is one of analogs/derivatives of C527, which is a novel and potent USP1 (ubiquitin-specific protease 1) inhibitor.IC50 Value: 0.544 uM (USP1) [1]Target: USP1Cells were treated with SJB2-043 for 24 hrs and cell extracts were incubated with HA-Ub-VS, followed by immunoblotting with anti-USP1 or anti-HA antibodies. Consistent with our previous studies and the most recent studies by Piatkov et al (24, 31, 33), USP1 in the untreated cells was detected on western blot as a doublet; full length USP1 and an auto-cleaved USP1 with only N-terminus. The Ub-USP1 conjugates were generated in the untreated cell lysates and were detected by an increase in molecular weight of USP1. However, the formation of the Ub-USP1 conjugate was inhibited by the addition of SJB2-043. Ub-aldehyde, a potent known nonspecific DUB inhibitor, caused a complete loss of USP1-Ub-VS conjugates in this competition assay. SJB2-043 inhibited the Ub-VS labeling of a limited number of endogenous DUB enzymes. In addition, SJB2-043 inhibited the labeling of USP1 with Ub-VS in a dose dependent manner [1].K562 leukemic cells were treated with SJB2-043, and survival and differentiation were assessed. SJB2-043 caused a dose-dependent decrease in the number of viable K562 cells, with an EC50 of approximately 1.07 uM± 0.08. Moreover, SJB2-043 induced apoptosis of K562 cells in a dose-dependent manner. Cytotoxic drug concentrations correlated with the concentrations required for ID1 degradation. In addition, low dose treatments with SJB2-043 activated differentiation of K562 cells into hemoglobin-expressing erythroid cells, as detected by benzidine staining.

Reference

[1]. Helena Mistry, Grace Hsieh, Sara S. Buhrlage, et al. Small molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol Cancer Ther Published OnlineFirst October 15, 2013.