Small molecule composition and application thereof in preparation of medicine for treating neuroblastoma

Abstract

The invention discloses a small molecule composition and an application of the small molecule composition in preparation of a medicine for treating neuroblastoma, and glycogen synthase kinase 3beta (Glygen synthase kinase 3beta, GSK-3beta) for promoting degradation of an MYC family member c-MYC has a function of promoting cancer progression in NB. The analysis on GSK-3beta substrate protein finds that the levels of N-MYC and Cyclin E1 protein and mRNA (messenger ribonucleic acid) are obviously reduced after the GSK-3beta is inhibited, and the level of anti-apoptotic protein MCL-1 is increased, so that the cell proliferation is obviously slowed down on the cell function. However, due to the fact that the detail of the MCL-1 protein level is enhanced, the cells are not subjected to obvious apoptosis under the treatment of a low-concentration GSK-3beta inhibitor. In subsequent experiments, the invention proves that the GSK-3beta inhibitor and the MCL-1 inhibitor cooperate to efficiently kill neuroblastoma for the first time.

Description

technical field [0001] The invention relates to the technical field of compositions for clinical treatment of tumors, in particular to the application of a GSK-3β inhibitor in conjunction with an MCL-1 inhibitor in efficiently killing neuroblastoma. Background technique [0002] Neuroblastoma (NB) is a malignant embryonal tumor originating from the neural crest and is the most common extracranial solid tumor in infants and young children. The incidence of NB is the third most common tumor in children, and it is the main cause of death from cancer in children aged 1-5 years. According to the INRG (International Neuroblastoma Risk Group Classification System), the five-year survival rate of patients with low-risk and intermediate-risk disease is close to 80%, but high-risk patients are still refractory after multiple intensive treatments, and more than 50% of children relapse, five The annual survival rate is only 40%-50%. The CCLE database shows that MYCN (encoding N-MYC pr...

AI Technical Summary

Problems solved by technology

However, the use of these approaches in the treatment of MYCN-amplified NB is enormously challenging due to the selectivity of such drugs for c-Myc or their impaired functional efficiency in vivo.

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