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9-ING-41, a Small-Molecule Glycogen Synthase kinase-3 Inhibitor, Is Active in Neuroblastoma

Andrey V Ugolkov, Gennadiy I Bondarenko, Oleksii Dubrovskyi, Ana P Berbegall, Samuel Navarro, Rosa Noguera, Thomas V O'Halloran, Mary J Hendrix, Francis J Giles, Andrew P Mazar

Anticancer Drugs. 2018 Sep;29(8):717-724.

PMID: 29846250

Abstract:

Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen synthase kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD-8, and 9-ING-41) suppressed the growth of neuroblastoma cells, whereas 9-ING-41, a clinically relevant small-molecule GSK-3β inhibitor with broad-spectrum preclinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and an increase in neuroblastoma cell apoptosis. Mouse xenograft studies showed that the combination of clinically relevant doses of CPT-11 and 9-ING-41 led to greater antitumor effect than was observed with either agent alone. These data support the inclusion of patients with advanced neuroblastoma in clinical studies of 9-ING-41, especially in combination with CPT-11.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42412521 XIAP Active human XIAP Active human Price
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