CX-4945 is an orally-available, ATP-competitive, pyridoquinoline-based inhibitor of CK2a with an IC50 potency of 1 nM and Ki of 0.38 nM. [1, 2] In a panel of 238 kinases at 500 nM, only 7 inhibited CK2 >90% [2] Treatment of BT474 and BxPC-3 cells with CX-4945 led to rapid dephosphorylation of CK2, Akt (S129), accompanied by reduction in phsophorylation at T308 and S473 of Akt. Since no reduction in PTEN phosphorylation at CK2's S370/S380, it is surmised that CX-4945 suppresses Pi3K/Akt signaling by directly blocking phosphorylation of Akt at Akt at S129 by CK2, rather than through activation of PTEN. [2]

Additionally, CX-4945 inhibits hypoxia-driven hypoxia inducible factor (HIF-1a) activity and prevents downregulation of pVHL and p53. CX-4945 also exerts a regulatory effect on the secretion of IL-6 in inflammatory breast cancer. [3]

CX-4945 may also be a potential sensitizer for resistant cells to conventional chemotherapeutic agents such as gemcitabine and cisplatin. [4]