| Description: |
NSC697923 is a potent UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13) inhibitor. NSC697923 induces neuroblastoma (NB) cell death via promoting nuclear importation of p53 in p53 wild-type NB cells. NSC697923 also induces cell death in p53 mutant NB cells by activation of JNK-mediated apoptotic pathway. NSC697923 inhibits DNA damage and NF-κB signaling. Antitumor activity[1][2]. |
| In Vivo: |
NSC697923 (5 mg/kg; i.p.; daily for 10 days) suppresses NB tumor growth in SH-SY5Y and NGP xenografts[1]. Animal Model: 5- to 6-week-old female athymic Ncr nude mice (orthotopic mouse model of NB; SH-SY5Y and NGP xenografts)[1] Dosage: 5 mg/kg Administration: I.p.; daily for 10 days Result: Significant tumor regression in both SH-SY5Y and NGP xenografts. |
| In Vitro: |
NSC697923 (0-5 μM; 24 hours) shows cytotoxic effect on NB cell lines[1]. NSC697923 (3 μM; 2 hours) can also induce apoptosis in p53 mutant NB cells by activation of JNK-mediated apoptotic pathway[1]. NSC697923 induces apoptosis in p53 wild-type NB cell lines by promoting p53 nuclear translocation and activation[1]. Cell Viability Assay[1] Cell Line: Three MYCN-amplified cell lines: IMR32, NGP, NB19 and three MYCN-non-amplified cell lines: CHLA-255, SK-N-AS, and SH-SY5Y Concentration: 0-5 μM Incubation Time: 24 hours Result: Significantly reduced NB cells viability in a dose-dependent manner. Also induced cell death in the p53 non-functional cell line SK-N-AS and p53 partially functional cell line NB-19. Western Blot Analysis[1] Cell Line: p53 wild-type SH-SY5Y and IMR32 cells Concentration: 3 μM Incubation Time: 2 hours Result: Induced expression of p53-targeted gene p21 as well as the cleavage of caspase 3 in two p53 wild-type cell lines SH-SY5Y and IMR32. |
| References: |
[1]. Cheng J, et al. A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways. Cell Death Dis. 2014;5(2):e1079. Published 2014 Feb 20.
[2]. Hodge CD, et al. Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting. ACS Chem Biol. 2015;10(7):1718-1728. |
