Silmitasertib sodium salt (CX-4945 sodium salt) is a potent and orally bioavailable, highly selective inhibitor of CK2(IC50 of 1 nM, CK2α).

CK2α:1 nM, CK2α:1 nM

Silmitasertib induces cytotoxicity and apoptosis, and exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways[3]. Silmitasertib (CX-4945) resultes in cell-cycle arrest and selectively induces apoptosis in cancer cells relative to normal cells, attenuates PI3K/Akt signalingand. The antiproliferative activity of Silmitasertib is correlated with expression levels of the CK2α catalytic subunit, attenuation of PI3K/Akt signaling[1]. Silmitasertib with PS-341 treatment prevents leukemic cells from engaging a functional UPR in order to buffer the PS-341-mediated proteotoxic stress in ER lumen, and decreases pro-survival ER chaperon BIP/Grp78 expression[2].

Silmitasertib (CX-4945), administered at doses of 25 or 75 mg/kg orally, was well tolerated and demonstrated strong antitumor effects alongside significant decreases in the mechanistic biomarker phospho-p21 (T145) in murine xenograft models[1].