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.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02829723	Advanced Solid Tumors	Phase 1 Phase 2	Recruiting	June 19, 2019	United States, Tennessee ... more >> Novartis Investigative Site Recruiting Nashville, Tennessee, United States, 37203 Contact: Jeremy Stewart    615-289-9227    jeremy.stewart@scresearch.net    Principal Investigator: Todd M. Bauer          United States, Texas Novartis Investigative Site Recruiting Houston, Texas, United States, 77030 Contact: Lacey McQuinn    713-563-9033    lmcquinn@mdanderson.org    Principal Investigator: Aung Naing          Novartis Investigative Site Recruiting San Antonio, Texas, United States, 78229 Contact: Kathleen Rodriguez    210-450-3838    rodriguezk3@uthscsa.edu    Principal Investigator: John Sarantopoulos          Italy Novartis Investigative Site Recruiting Rozzano, MI, Italy, 20089 Japan Novartis Investigative Site Recruiting Nagoya, Aichi, Japan, 466 8560 Singapore Novartis Investigative Site Recruiting Singapore, Singapore, 169610 Spain Novartis Investigative Site Recruiting Hospitalet de LLobregat, Catalunya, Spain, 08907 Taiwan Novartis Investigative Site Recruiting Taipei, Taiwan, 10002 Collapse <<