Glioblastoma multiforme (GBM) is the most prevalent type and lethal form of primary malignant
brain tumor, accounting for about 40-50% of intracranial
tumors and without effective treatments now. Cell reprogramming is one of the emerging treatment approaches for GBM, which can reprogram
glioblastomas into non-
tumor cells to achieve
therapeutic effects. However,
anti-GBM drugs through reprogramming can only provide limited symptom relief, and cannot completely cure GBM. Here we showed that
PT109, a novel multi-
kinase inhibitor, suppressed GBM's proliferation, colony formation, migration and reprogramed GBM into oligodendrocytes. Analysis of quantitative proteomics data after
PT109 administration of human GBM cells showed significant influence of energy metabolism, cell cycle, and immune system processes of GBM-associated
protein. Metabolomics analysis showed that
PT109 improved the aerobic respiration process in
glioma cells. Meanwhile, we found that
PT109 could significantly increase the ratio of
Pyruvate kinase M1/2 (PKM1/2) by reducing the level of
polypyrimidine tract-binding protein 1 (PTBP1). Altogether, this work developed a novel
anti-GBM small molecule
PT109, which reprogramed GBM into oligodendrocytes and changed the metabolic pattern of GBM through the PTBP1/PKM1/2 pathway, providing a new strategy for the development of anti-
glioma drugs.