NSC 632839 inhibits purified USP2- and USP7-mediated cleavage of Ub-PLA2. NSC 632839 does not inhibit the reporter enzyme PLA2 over the concentration range tested (1.2–150 μM), indicating that the reported inhibition is selective for isopeptidases. NSC 632839 is capable of sustaining caspase-3/caspase-7 activity in the absence of a functional caspase-9 in E1A and E1A/C9DN cells. NSC 632839 induces apoptosis with IC50 of 15.65 μM and 16.23 μM in E1A and E1A/C9DN cells, respectively. NSC-632839 (10 μM) provokes the accumulation of polyubiquitins in E1A cells expressing HA-tagged ubiquitin. NSC-632839 (10 μM) dramatically increases the levels of Noxa and Mcl-1 in E1A cells during a time course analysis. NSC-632839 (10 μM) provokes mitochondrial fragmentation in a higher percentage of cells with an intact outer mitochondrial membrane compared with etoposide.
