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].
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.