生物活性 | |||
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描述 | The inhibition of CSF-1R, which can deplete macrophages and reduce tumor volume, is an effective strategy to treat for glioblastoma multiforme because of the crucial function of CSF-1R through the paracrine CSF-1–EGF signaling loop in glioma microenvironment forming by the tumor-associated macrophages and microglia (TAMs). BLZ945 is a potent, selective and a brain-penetrant inhibitor of CSF-1R with IC50 value of 1nM (measured by enzymatic activity). The CSF-1–dependent proliferation of wild-type bone marrow–derived macrophages, also pCSF-1R-Y721 induced by CSF-1, can be inhibited by BLZ945 with EC50 value of 67nM. The in vivo study showed that treatment with BLZ945 can substantially decreased microglia numbers in normal brains but not tumor-associated macrophages and microglia in PDGF-B–driven glioma (PDG) mice because of the promotion of TAMs survival by glioma-supplied factors. However, TAMs can be functionally altered in BLZ945 treated gliomas because of the loss of M2 polarization and the enhancement of phagocytosis. Oral dose of 200mg/kg BLZ945 once daily improved survival and decreases glioma malignancy in the transgenic PDG model, with blocking of glioma progression and increased apoptosis[1]. |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.51mL 0.50mL 0.25mL |
12.55mL 2.51mL 1.25mL |
25.10mL 5.02mL 2.51mL |