Background:

CX-4945 (Silmitasertib) is a potent and selective casein kinase 2 (CK2) inhibitor with IC50 value of 1 nM. It is ATP-competitive and can be taken orally [1].

CX-4945 has been reported to have antiproliferative activity against a wide range of tumor cell lines. It is suggested that CX-4945 suppresses the CK2 regulated PI3K/Akt signaling pathway by inhibiting Akt phosphorylation at Serine 129, but not by activating PTEN. Additionally, cells treated with CX-4945 had a reduction of p21 phophorylation and an up-regulations of total p21 and p27. CX-4945 has been shown to induce cell-cycle arrest at G2/M phase in breast cancer cell line BT-474. It also causes cell-cycle arrest at G1 phase the breast cancer cell line BxPC-3) [1].

In CX-4945 and BxPC-3 derived mouse xenograft model, CX-4945 induced a reduction of phos-p21 expression along with anti-carcinoma effects [1]

参考文献:
[1] Siddiqui-Jain A1,?Drygin D,?Streiner N,?Chua P,?Pierre F,?O'Brien SE,?Bliesath J,?Omori M,?Huser N,?Ho C,?Proffitt C,?Schwaebe MK,?Ryckman DM,?Rice WG,Anderes K. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res.?2010 Dec 15;70(24):10288-98.