生物活性

• 描述It is found that macrophage colony-stimulating factor is important for the differentiation of osteoclasts, thus facilitating it to participate into the development of osteolysis in bone metastatic lesions. Ki20227 is an inhibitor of c-fms tyrosine kinase with IC50 values of 2nM, also showed inhibition against VEGFR2 with IC50 value of 12nM (measured by kinase activity). In cellular study, Ki20227 (>3nM) showed dose-dependent inhibition of M-CSF-dependent c-Fms phosphorylation in RAW264.7 cells cultured in medium supplemented with 0.1% FCS. Also it showed inhibitory activity against M-CSF-dependent and VEGF-dependent cell growth in M-NFS-60 (10-100nM) and HUVEC cells (300-3000nM). As macrophage colony-stimulating factor was important in osteolysis, inhibition of c-Fms kinase by Ki20227 at concentration of 100nM suppressed the development of TRAP-positive osteoclast-like cell formation. Oral administration of 50 mg/kg of Ki20227 daily for 20 days could markedly decrease the osteolytic lesion areas which caused by metastasizing A375 cells in nude rats. Once daily oral treatment with Ki20227 at 20 mg/kg for 28 days significantly reduced the TRAP-positive osteoclastic cells on the bone surface in the primary spongiosa in ovariectomized rats, which suggesting Ki20227 could also suppress TRAP-positive osteoclast-like cell development in a non-tumor-bearing rodent model^[1].
• 作用机制Not found

• 动物研究
  剂量	Nude rat[1] (p.o.): 10 mg/kg - 50 mg/kg
  给药途径	p.o.