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Biological Activity:

NSC697923 is a cell permeable, potent and selective inhibitor of the Ub-conjugating enzyme (E2) complex Ubc13-Uev1A. It selectively inhibits PMA-induced NF-κB activation, and also inhibits IκBα phosphorylation by both RANKL and LPS. It impedes the formation of the Ubc13 and ubiquitin thioester conjugate and suppresses constitutive NF-κB activity in ABC-DLBCL cells. It inhibits the proliferation and survival of ABC-DLBCL cells and GCB-DLBCL cells, suggesting the Ubc13-Uev1A may be crucial for DLBCL growth. In neuroblastoma (NB) cell lines, NSC697923 shows cytotoxic effect, and inhibits both anchorage-dependent and -independent colony formation. It also shows in vivo antitumor efficacy in NB orthotopic xenografts.

How to Use:

• In vitro:  NSC697923 was used at 1-5 µM final concentration in various in vitro assays.
• In vivo:  NSC697923 was administered by IP injection at 10 mg/kg once per day in SH-SY5Y and NGP xenografts.

Reference: 

1. 1. Pulvino M, et al. Inhibition of proliferation and survival of diffuse large B-cell lymphoma cells by a small-molecule inhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A. (2012) Blood. 120(8):1668-77.
2. 2. Cheng J, et al. A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways. (2014) Cell Death Dis. 5:e1079.