EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #72472_C
CSF-1 通路抑制剂；抑制 cFMS
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总览
GW2580 是 cFMS 激酶的选择性抑制剂 (IC₅₀ = 0.03 μM)（Conway et al., 2008），可阻断其自身磷酸化集落刺激因子 (CSF-1 或 M-CSF) 的能力，而集落刺激因子可促进巨噬细胞的存活、增殖和分化。
分化
·证实 CSF-1 在促进小鼠造血干细胞髓系谱系偏向中的重要性 （Mossadegh-Keller et al.）。
·证实 CSF-1 在小鼠和人类巨噬细胞集落及单核细胞扩增中的重要性(He et al.; Clanchy et al.; Conway et al., 2008; Conway et al., 2005)。
·抑制人破骨细胞培养物、大鼠颅盖骨和大鼠胎儿长骨（Conway et al., 2005），以及小鼠关节炎模型（Conway et al., 2008）中的骨质退化。
细胞类型
间充质干/祖细胞，髓系细胞，成骨细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
应用
分化
研究领域
疾病建模，干细胞生物学
CAS 编号
870483-87-7
化学式
C₂₀H₂₂N₄O₃
纯度
≥98%
通路
CSF-1
靶点
cFMS
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
相关材料与文献
技术资料 (1)
文献 (5)
Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580.
Proceedings of the National Academy of Sciences of the United States of America 2005 NOV
Abstract
Colony-stimulating-factor-1 (CSF-1) signaling through cFMS receptor kinase is increased in several diseases. To help investigate the role of cFMS kinase in disease,we identified GW2580,an orally bioavailable inhibitor of cFMS kinase. GW2580 completely inhibited human cFMS kinase in vitro at 0.06 microM and was inactive against 26 other kinases. GW2580 at 1 microM completely inhibited CSF-1-induced growth of mouse M-NFS-60 myeloid cells and human monocytes and completely inhibited bone degradation in cultures of human osteoclasts,rat calvaria,and rat fetal long bone. In contrast,GW2580 did not affect the growth of mouse NS0 lymphoblastoid cells,human endothelial cells,human fibroblasts,or five human tumor cell lines. GW2580 also did not affect lipopolysaccharide (LPS)-induced TNF,IL-6,and prostaglandin E2 production in freshly isolated human monocytes and mouse macrophages. After oral administration,GW2580 blocked the ability of exogenous CSF-1 to increase LPS-induced IL-6 production in mice,inhibited the growth of CSF-1-dependent M-NFS-60 tumor cells in the peritoneal cavity,and diminished the accumulation of macrophages in the peritoneal cavity after thioglycolate injection. Unexpectedly,GW2580 inhibited LPS-induced TNF production in mice,in contrast to effects on monocytes and macrophages in vitro. In conclusion,GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes.
Effects of the cFMS kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) in normal and arthritic rats.
The Journal of pharmacology and experimental therapeutics 2008 JUL
Abstract
The cFMS (cellular homolog of the V-FMS oncogene product of the Susan McDonough strain of feline sarcoma virus) (Proc Natl Acad Sci U S A 83:3331-3335,1986) kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) inhibits colony-stimulating factor (CSF)-1-induced monocyte growth and bone degradation in vitro and inhibits CSF-1 signaling through cFMS kinase in 4-day models in mice (Proc Natl Acad Sci U S A 102:16078,2005). In the present study,the kinase selectivity of GW2580 was further characterized,and the effects of chronic treatment were evaluated in normal and arthritic rats. GW2580 selectively inhibited cFMS kinase compared with 186 other kinases in vitro and completely inhibited CSF-1-induced growth of rat monocytes,with an IC(50) value of 0.2 microM. GW2580 dosed orally at 25 and 75 mg/kg 1 and 5 h before the injection of lipopolysaccharide inhibited tumor necrosis factor-alpha production by 60 to 85%,indicating a duration of action of at least 5 h. In a 21-day adjuvant arthritis model,GW2580 dosed twice a day (b.i.d.) from days 0 to 21,7 to 21,or 14 to 21 inhibited joint connective tissue and bone destruction as assessed by radiology,histology and bone mineral content measurements. In contrast,GW2580 did not affect ankle swelling in the adjuvant model nor did it affect ankle swelling in a model where local arthritis is reactivated by peptidoglycan polysaccharide polymers. GW2580 administered to normal rats for 21 days showed no effects on tissue histology and only modest changes in serum clinical chemistry and blood hematology. In conclusion,GW2580 was effective in preserving joint integrity in the adjuvant arthritis model while showing minimal effects in normal rats.
HUVEC co-culture and haematopoietic growth factors modulate human proliferative monocyte activity.
Cytokine 2012 JUL
Abstract
Monocytes and macrophages are often claimed to have limited potential for proliferation in vivo and in vitro although a human monocyte subset with increased potential to proliferate in culture,termed the proliferative monocyte (PM),has previously been identified. The response of the putatively less mature PM to conditions conducive to haematopoietic stem cell culture was determined. Co-culture of monocytes on a HUVEC monolayer induced up to four cell divisions in a 9 day period. The PM response to haematopoietic growth factors (Flt3L,SCF,IL-6,IL-3 and M-CSF) was determined. M-CSF induced the greatest proliferative response in PM; IL-3 and Flt3L reduced basal and M-CSF-induced proliferation. The inhibition of M-CSFR kinase activity by GW2580 indicated that the ligand(s) for this receptor was a potent inducer of proliferation of this subset; inhibitors of intracellular signalling pathways also reduced PM proliferation.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 870483-87-7 |
| Chemical Formula | C₂₀H₂₂N₄O₃ |
| 纯度 | ≥ 98% |
| Target | cFMS |
| Pathway | CSF-1 |
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