GENZ-882706 (RA03546849) 是一种有效的集落刺激因子-1 受体 (CSF-1R) 抑制剂，提取自专利 WO 2017015267A1。
GENZ-882706 is a potent colony stimulating factor-1 receptor (CSF-1R) Inhibitor extracted from patent WO 2017015267A1.
Genz-882706 induces an increased level of proliferative activity on unstimulated cells 48 hours post treatment and the reason for this effect is unclear[1].
Daily treatment with Genz-882706 significantly reduces experimental autoimmune encephalomyelitis. Treatment with Genz-882706 in experimental autoimmune encephalomyelitis (EAE) mice results in significant decreases in MCP-1, IL-6, IL-Ιβ and IP-10 levels in spinal cord homogenates when compared to Vehicle treated animals. Treatment with Genz-882706 shows a significant increase in TNF-a levels in the spinal cord when compared to the vehicle treated group. Genz-882706 at both the 30 mg/kg and the 100 mg/kg dose significantly reduces the number of microglia and monocytes/macrophages in the brain and spinal cord compared to the vehicle and LPS controls. Treatment with Genz-882706 modestly reduces CD80 expression on monocytes/macrophages in the brain[1].
[1]. Kane, et al. Colony Stimulating Factor-1 Receptor (CSF-1R) Inhibitors. WO 2017015267A1
Cell experiment: | To determine the effect of GENZ-882706 on the proliferation of primary murine microglial cells following LPS or CSF-1 stimulation, GENZ-882706 (500 nM) is added to appropriate assay wells. 25 μL medium are also added to all cells only wells at this time. 25 μL of LPS at 10 ng/mL or 100 ng/mL or CSF-1 at 100 ng/mL are then added to appropriate wells. 25 μL of medium are added to wells not receiving LPS or CSF-1 to bring the final volume of all assay wells to 150uL[1]. |
Animal experiment: | Mice[1]Mycobacterium tuberculosis is induced in a secondary progressive experimental autoimmune encephalomyelitis (EAE) model in NOD mice with an emulsion of MOG 35-55 and CFA. Therapeutic treatment with Genz-882706 (25mg/kg/day) or vehicle control is started on Day 27 post-disease induction when mice began to enter the progressive stage of disease. Inflammatory/neurotoxic mediators in the CNS are measured through protein analysis in homogenate and gene expression[1]. |
参考文献: [1]. Kane, et al. Colony Stimulating Factor-1 Receptor (CSF-1R) Inhibitors. WO 2017015267A1 | |
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