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Overview
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Background
The IC50s of Ki20227 inhibiting c-Fms, stem cell factor receptor (c-Kit), vascular endothelial growth factor receptor-2 (KDR), and platelet-derived growth factor receptor B were found to be 2, 451, 12, and 217 nmol/L, respectively.
Macrophage colony-stimulating factor (M-CSF) is required for the development of individual mononuclear phagocyte populations and is involved in the immune response. Ki20227 (N-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl] urea) is a highly selective M-CSF receptor (c-fms) tyrosine kinase inhibitor.
In vitro: Ki20227 was found to inhibit c-Fms, KDR, c-Kit, and platelet-derived growth factor receptor B, but not inhibit other kinases tested, such as epidermal growth factor receptor, fms-like tyrosine kinase-3 , or c-Src. Ki20227 was also found to inhibit the M-CSF dependent growth of M-NFS-60 cells but not the M-CSF independent growth of A375 human melanoma cells. Furthermore, Ki20227 inhibited the development of tartrate-resistant acid phosphatase-positive osteoclast-like cells in a dose-dependent manner [1].
In vivo: Oral administration of Ki20227 suppressed osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. In addition, Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats [1].
Clinical trial: Ki20227 is currently in the preclinical developlent stage and no clinical data are available.
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