MRT00033659 is a potent broad-spectrum kinase inhibitor of CK1 (IC50=0.9 µM for CK1δ) and CHK1 (IC50=0.23 µM). MRT00033659, a pyrazolo-pyridine analogue, induces p53 pathway activation and E2F-1 destabilisation[1].
MRT00033659 (5-40 µM; 48 hours) is sufficient to significantly reduce cell number of 5 µM[1]. MRT00033659 (1-80 µM; 48 hours) induces substantial cell death from 5 µM[1]. MRT00033659 (0.2-80 µM; 48 hours) induces a robust and sustained stabilisation of p53, MDM2 and p21 proteins, as well as E2F-1 destabilisation from 0.2 µM to 5 µM[1]. MRT00033659 does not inhibit p38α MAPK[1]. Cell Viability Assay[1] Cell Line: A375 cells
[1]. Huart AS, et al. A Casein kinase 1/Checkpoint kinase 1 pyrazolo-pyridine protein kinase inhibitor as novelactivator of the p53 pathway. Bioorg Med Chem Lett. 2013 Oct 15;23(20):5578-85.