CP681301 is a potent inhibitor of CDK5 with antiproliferative activity. CP681301 exhibits anti-tumor activity in Drosophila. CP681301 decreases the expression of CD133, OLIG2, SOX2, KI67, pCDK5 protein level in Glioma stem cells (GSCs). CP681301 reduces self-renewal in mouse glioma xenografts [1].

CP681301, at a concentration of 1 μM for a duration of 96 hours, exhibits variable cytotoxic effects on GSC (glioblastoma stem cell) cultures without being toxic to NHNPs (normal human neuro-progenitors) [1]. Furthermore, treatment with CP681301 in concentrations of 0, 10, and 50 μM for 48 hours results in the decreased expression of stem cell markers CD133, OLIG2, SOX2, the proliferation marker KI67, and the pCDK5 protein level in GSCs [1]. Additionally, CP681301 at concentrations of 0, 0.5, and 1 μM effectively suppresses CREB Ser133 phosphorylation, indicating a potential inhibition of signaling pathways involved in GSC proliferation and survival [1]. The cytotoxicity assay and western blot analysis conducted on various cell lines, including NHNP, N12.159, GBM121, GBM39, and N08-74 cells, further support these findings, highlighting CP681301's selective toxicity to GSCs over NHNPs and its role in modulating key regulatory proteins and markers associated with GSCs' stemness and proliferation characteristics [1].

CP681301, administered at a concentration of 1 mM and fed over a period of 10 days, demonstrates effective anti-tumor properties in 0- to 2-day-old adult Drosophila models exhibiting brat-RNAi tumors. This treatment notably reduces the activity of phospho-dCdk5 (Y15) within tumor cells and diminishes the self-renewal capacity of stem cells. Additionally, it promotes the expression of the neuronal marker ElaV in the affected cells, contributing to a significant 2.8-fold increase in median survival.