Description
Ki20227 is an inhibitor of macrophage colony stimulating factor 1 (CSF1) receptor tyrosine kinase (c-Fms; IC
50 = 2 nM).
1 It inhibits CSF1-dependent c-Fms phosphorylation in a dose-dependent manner in RAW264.7 cells and reduces CSF1-dependent growth of M-NFS-60 cells (IC
50 = 14 nM). Ki20227 suppresses development of TRAP-positive osteoclast-like cells from murine bone marrow (IC
50 = 40 nM) and decreases the number and area of osteolytic lesions on femurs and tibiae in a murine A375 subcutaneous xenograft model. Ki20227 also reduces TNF-α infiltration and osteolytic bone destruction in a collagen-induced arthritis (CIA) mouse model.
2
Uses
Ki 20227 is a c-fms tyrosine kinase inhibitor, which suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model.
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].
References
[1] ohno h, kubo k, murooka h, kobayashi y, nishitoba t, shibuya m, yoneda t, isoe t. a c-fms tyrosine kinase inhibitor, ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. mol cancer ther. 2006;5(11):2634-43.
