NSC697923

[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].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> E1/E2/E3 Enzyme

[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.

[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.

[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.

[ Molecular Formula ]:
C₁₁H₉NO₅S

[ Molecular Weight ]:
267.25800

[ Exact Mass ]:
267.02000

[ PSA ]:
101.48000

[ LogP ]:
3.93300

[ Appearance of Characters ]:
white to beige

[ Storage condition ]:
?20°C

[ Water Solubility ]:
DMSO: soluble20mg/mL, clear

Click to get detail MSDS

[ Symbol ]:

GHS05, GHS07

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H318

[ Precautionary Statements ]:
P280-P305 + P351 + P338

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22-41

[ Safety Phrases ]:
26-39

[ RIDADR ]:
NONH for all modes of transport

Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting.

ACS Chem. Biol. 10(7) , 1718-28, (2015)

Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, N...

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