cx-4945 and Osteoporosis

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.

Topics: Animals; Bone Morphogenetic Protein 2; Casein Kinase II; Cell Differentiation; Cell Line; Humans; Mice; Naphthyridines; Osteoblasts; Osteoclasts; Osteoporosis; Phenazines; Phosphorylation; RANK Ligand; Signal Transduction