NSC697923 is a potent, cell-permeable UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13) inhibitor. NSC697923 induces cell death by promoting nuclear import of p53 or activating the JNK-mediated apoptotic pathway. NSC697923 can be used in studies related to neuroblastoma and diffuse large B-cell lymphoma (DLBCL)[1-4].
In vitro, NSC697923 (0.5-2μM) was used to treat ABC-DLBCL cells, GCB-DLBCL cells, and primary DLBCL cells for 24 hours. NSC697923 significantly inhibited cell proliferation and survival, while inducing apoptosis[5]. NSC697923 (0.1-0.5μM) was used to treat neuroblastoma cell lines (including SH-SY5Y, IMR32, SK-N-AS, LA-N-6, etc.) for 24 hours. NSC697923 significantly induced apoptosis, while inhibiting cell proliferation and colony formation[6].
In vivo, NSC697923 (5mg/kg) was intraperitoneally injected every other day into NSG SCID mice bearing A375 xenograft tumors for 18 days. NSC697923 significantly reduced subcutaneous tumor growth[7]. NSC697923 (3mg/kg; three times per week) combined with Ramipril (2mg/kg; three times per week) was intraperitoneally injected into STZ-induced diabetic DBA/2J mice for 6 weeks. NSC697923 significantly reduced the accumulation of K63-ubiquitinated proteins, renal fibrosis, and glomerulosclerosis[8].
References:
[1] Gombodorj N, Yokobori T, Yoshiyama S, et al. Inhibition of Ubiquitin-conjugating Enzyme E2 May Activate the Degradation of Hypoxia-inducible Factors and, thus, Overcome Cellular Resistance to Radiation in Colorectal Cancer. Anticancer Res. 2017 May;37(5):2425-2436.
[2] Hodge CD, Edwards RA, Markin CJ, et al. Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting. ACS Chem Biol. 2015 Jul 17;10(7):1718-28.
[3] Zhang K, Zhao Y, Chen X, et al. p53 promote oxidative stress, neuroinflammation and behavioral disorders via DDIT4-NF-κB signaling pathway. Redox Biol. 2025 Oct;86:103836.
[4] Cao DY, Zhang ZH, Li RZ, et al. A small molecule inhibitor of caspase-1 inhibits NLRP3 inflammasome activation and pyroptosis to alleviate gouty inflammation. Immunol Lett. 2022 Apr;244:28-39.
[5] Pulvino M, Liang Y, Oleksyn D, 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. Blood. 2012 Aug 23;120(8):1668-77.
[6] Cheng J, Fan YH, Xu X, et al. A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways. Cell Death Dis. 2014 Feb 20;5(2):e1079.
[7] Dikshit A, Jin YJ, Degan S, et al. UBE2N Promotes Melanoma Growth via MEK/FRA1/SOX10 Signaling. Cancer Res. 2018 Nov 15;78(22):6462-6472.
[8] Pontrelli P, Conserva F, Menghini R, et al. Inhibition of Lysine 63 Ubiquitination Prevents the Progression of Renal Fibrosis in Diabetic DBA/2J Mice. Int J Mol Sci. 2021 May 14;22(10):5194.