CX-4945

CX-4945 (Silmitasertib, CX4945) is a potent, selective, orally bioavailable, ATP-competitive inhibitor of protein kinase Casein Kinase 2 (CK2) with Ki of 0.38 nM, CK2α IC50 of 1 nM; displays good selectivity profile against a panel of 238 kinases; attenuates PI3K/Akt signaling, blocks CK2-dependent HIF-1α transcription, caused cell cycle arrest and selectively induces apoptosis in cancer cells relative to normal cells; exhibits antitumor efficacy in murine xenograft models.Blood Cancer Phase 2 Clinical (In Vitro) :Silmitasertib (CX-4945) causes cell-cycle arrest and selectively induces apoptosis in cancer cells relative to normal cells, attenuates PI3K/Akt signalingand, and the antiproliferative activity of Silmitasertib (CX-4945) is correlated with expression levels of the CK2α catalytic subunit, Attenuation of PI3K/Akt signaling. Silmitasertib (CX-4945) 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. Silmitasertib (CX-4945) 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. (In Vivo) :Silmitasertib (CX-4945) (25 or 75 mg/kg, p.o.) is well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145) in murine xenograft models.