title: The protein kinase 2 inhibitor CX-4945 regulates osteoclast and osteoblast differentiation in vitro.
abstract: Drug repositioning can identify new therapeutic applications for existing drugs, thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945 regulates human cancer cell survival and angiogenesis. Here we found that CX-4945 significantly inhibited the RANKL-induced osteoclast differentiation, but enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX-4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression accompanied with suppression of Akt phosphorylation, but in contrast, it enhanced the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus a novel drug candidate for bone-related disorders such as osteoporosis.
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacological Research Center, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Korea.
authors.forename: You Hwa
authors.initials: YH
authors.lastname: Son
authors.forename: Seong Hee
authors.initials: SH
authors.lastname: Moon
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D051379:Mice; D009287:Naphthyridines / Q000494:pharmacology* / Q000627:therapeutic use; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D010619:Phenazines; D010766:Phosphorylation; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D055396:Bone Morphogenetic Protein 2; D009287:Naphthyridines; D010619:Phenazines; D053245:RANK Ligand; C555142:silmitasertib; D047390:Casein Kinase II