Cell lines

Human NB cell lines with MYCN amplification (IMR-32, NGP and NB-19) and without (CHLA-255, SK-N-AS and SH-SY5Y)

Preparation method

The solubility of this compound in DMSO is >10mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

5μM ;24hours

Applications

Treatment with NSC697923 significantly reduced NB cells viability in a dose-dependent manner and inhibited both anchorage-dependent and -independent colony formation of NB cells. NSC697923 induced apoptosis in all NB cell lines tested. In addition, NSC697923 also induced apoptosis in p53 mutant NB cells by activation of JNK-mediated apoptotic pathway. NSC697923 exhibited its effect primarily through inducing p53 nuclear translocation but not increasing its total amount. NSC697923 treatment also induced more phosphorylation of JNK, p38, and ERK in SK-N-AS.

Animal models

5- to 6-week-old female athymic Ncr nude mice (SH-SY5Y and NGP xenografts)

Dosage form

5 mg/kg , intraperitoneal injection everyday for 10 days

Application

These results showed significant tumor regression in NSC697923 treatment group of both SH-SY5Y and NGP xenografts.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

NSC697923 is a selective and permeable inhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A which blocks the formation of ubiquitin thioester conjugate. And the small-molecule inhibitor inhibits proliferation and survival of diffuse large B-cell lymphoma cells (DLBCL) [1].

Diffuse large cell lymphoma is the most common lymphoma that has a rapid growth rate and causes masses infiltrating tissues or obstructing organs. Unless treated in time, it will kill people quickly.

NSC697923 is an potent inhibitor of the formation of the Ubc13 and NF-κB activation in DLBCL. There are constitutive NF-kB pathway activities in DLBCL. So, impeding NF-kB activation in DLBCL would be a good solution to inhibit the proliferation and survival of diffuse of DLBCL. Also, NSC697923 blocks the formation of the Ubc13-Uev1A by inhibiting the formation of the Ubc13_Ub conjugate while it is a key component for DLBCL grown. In the long term, the cell cannot survive without Ubc13 expression. In conclusion, compound NSC697923 is an efficient inhibitor of DLBAL survival [1,2].

In a xenograft mouse model, NSC697923 has significantly reduced the proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and induces NB cell death [1,3].

References:
[1].  Pulvino M, Liang Y, Oleksyn D, et al. Inhibition of proliferation and survival of diffuse large B-cell lymphoma cells by a small-moleculeinhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A. Blood, 2012, 120: 1668–1677.
[2].  Zhaojia Wu, Siqi Shen, Zhiling Zhang, et al. Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-кB mediated matrix metalloproteinase-1 gene regulation. Breast Cancer Research, 2014, 16:75-90.
[3].  J Cheng, Y-H Fan, X Xu, et al. A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways. Cell Death and Disease, 2014, 54: 1079.