title: Druggability of the CK2 inhibitor CX-4945 as an anticancer drug and beyond.
abstract: Casein kinase 2 (CK2) is involved in multiple cellular processes such as proliferation, apoptosis, and cell cycle. In particular, its over-expression in human cancers is associated with angiogenesis and tumor progression. As a first orally bioavailable small molecule inhibitor of CK2, CX-4945 exerts anti-proliferative activity in human cancer cells by inhibiting the cell cycle and the PI3K/Akt signaling pathway. Additionally, CX-4945 reduces angiogenesis via blockade of hypoxia-inducible factor-1α transcription and suppresses the inflammatory interleukin-6 production in human breast cancer cells. These effects are supported by results from mouse xenograft model investigations. Here, we discuss the druggability of CX-4945 and its potential to be developed as an anti-cancer drug in clinical trials.
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009287:Naphthyridines / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010619:Phenazines; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D009287:Naphthyridines; D010619:Phenazines; C555142:silmitasertib; D047390:Casein Kinase II