Biological Activity:CX-4945 (Silmitasertib) is a potent, selective and bioavailable CK2 (Casein Kinase 2) Inhibitor with IC50 of 1 nM. It only inhibits 7 of the 238 kinases by more than 90% at concentration of 0.5 μM, which is 500-fold selectivity over CK2. Although in cell-free systems CX-4945 inhibits FLT3, PIM1, and CDK1 with IC50 of 35 nM, 46 nM, and 56 nM, respectively, but it is inactive against FLT3, PIM1, and CDK1 in cell-based functional assays at 10 µM. CX-4945 exhibits a broad spectrum of antiproliferative activity, correlates with CK2α mRNA and protein levels but not the CK2α' catalytic subunit, the regulatory CK2β subunit, and the PI3K/Akt or PTEN mutational status. Combined inhibition of EGFR and CK2 augments the attenuation of PI3K-Akt-mTOR signaling and the killing of cancer cells. CX-4945 can potentiate senescence by blocking tumour progression in Ptenpc -/- mice. Now CX-4945 is in phase I/II clinical trials to treat cancer. How to Use:In vitro: CX-4945 was used at 1 µM final concentration in various in vitro assays.In vivo: Oral administration of CX-4945 at 25 mg/kg or 75 mg/kg twice daily displays potent antitumor activity in the BT-474 model, with TGI of 88% and 97%, respectively. In PC3 xenograft model, administration of CX-4945 at 25 mg/kg, 50 mg/kg, or 75 mg/kg causes tumor growth inhibition with TGI of 19%, 40%, and 86%, respectively.Reference:
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