CP681301

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

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

CP681301 (1 µM; 96 h) shows variably cytotoxic to the tested GSC cultures but is not toxic to NHNPs[1]. CP681301 (0, 10, 50 µM; 48 h) decreases the expression of CD133, OLIG2, SOX2, KI67, pCDK5 protein level in GSCs[1]. CP681301 (0, 0.5, 1 µM; ) suppresses the expression of CREB Ser133 phosphorylation[1]. Cell Cytotoxicity Assay[1] Cell Line: NHNP, N12.159, GBM121, GBM39, N08-74 cells Concentration: 1 µM Incubation Time: 96 h Result: Showed variably cytotoxic to the tested GSC cultures but was not toxic to NHNPs (normal human neuro-progenitors). Western Blot Analysis[1] Cell Line: GBM 121, GBM39 cells Concentration: 1 µM Incubation Time: 48 h Result: Suppressed the expression of CD133, OLIG2, and SOX2 and cell proliferation marker KI67.

CP681301 (1 mM; fed; 10 days) shows anti-tumor activity in 0- to 2-day-old adult Drosophila[1]. Animal Model: 0- to 2-day-old adult Drosophila (brat-RNAi tumors)[1] Dosage: 1 mM Administration: Fed, 10 days Result: Reduced active phospho-dCdk5 (Y15) in tumor cells and the self-renewal properties of stem cells, increased the expression of neuronal marker ElaV in these cells and increased the median survival by 2.8-fold.

[1]. Mukherjee S, et al. CDK5 Inhibition Resolves PKA/cAMP-Independent Activation of CREB1 Signaling in Glioma Stem Cells. Cell Rep. 2018 May 8;23(6):1651-1664.