Description
NSC-632839 (157654-67-6) is a pan-specific ubiquitin isopeptidase inhibitor. (IC50= 45, 37 and 9.8 μM for USP2, USP7 and SENP2 respectively) Does not effect proteasome proteolytic activity. NSC-632839 induces apoptosis via a Bcl-2-dependent but apoptosome-independent mitochondrial pathway.1,2?Cell permeable.
Uses
Protein ubiquitination is a dynamic process that can be reversed by deubiquitinating enzymes (DUBs) that remove ubiquitin from proteins, sparing them from degradation by the proteasome. The DUBs have been divided into various groups, the largest being the ubiquitin-specific proteases (USPs). NSC 632839 inhibits USP2 and USP7 as well as the ubiquitin-like SUMO peptidase SENP2 with EC50 values of 45, 37, and 9.8 μM, respectively. It is reported to inhibit apoptosis through a Bcl-2-dependent and apoptosome-independent pathway of caspase activation (IC50 = 15.7 μM in cells sensitized by E1A, an adenoviral oncogene).
Biological Activity
Inhibitor of ubiquitin isopeptidase activity that displays no effect on the proteolytic activity of the proteasome. Induces apoptosis via a Bcl-2-dependent and apoptosome-independent pathway of caspase activation (IC 50 values are 15.65 and 16.23 μ M in E1A and E1A/C9CN cells respectively).
References
1) Aleo et al. (2006), Identification of new compounds that trigger apoptosome-independent caspase activation and apoptosis; Cancer Res., 66 9235
2) Nicholson et al. (2008), Characterization of ubiquitin and ubiquitin-like-protein isopeptidase activities; Protein Sci. 17 1035
