生物活性

• 靶点	c-FMS IC50:1nM

• 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].

• 动物研究
  剂量	Mice: 7 mg/kg - 169 mg/kg[2] (p.o.), 2.5 mg/kg[3] (i.v.) Rat: 10 mg/kg - 150 mg/kg[4] (p.o.) Monkey: 10 mg/kg - 100 mg/kg[4] (p.o.)
  给药途径	p.o., i.v.