GW2580 is a selective CSF-1R inhibitor for c-FMS with IC50 of 30 nM, 150- to 500-fold selective compared to b-Raf, CDK4, c-KIT, c-SRC, EGFR, ERBB2/4, ERK2, FLT-3, GSK3, ITK, JAK2 etc.
GW2580 is a selective inhibitor of CSF-1R with IC50 value of 60nM for cFMS kinase (measured by kinase activity), 150- to 500-fold selective compared to the other kinase tested including BRAF, CDK4, cKIT, cSRC, EGFR, ERBB2, ERBB4, ERK2, FLT-3, GSK3, ITK, JAK2, JNK3, MK2, P38, PDGFR-β, PDHK4, PKA, PKCα, PKCβI, PKCζ, SYK, TIE2 and VEGFR2, as well as mouse LCK kinases. Complete inhibition of CSF-1-dependent growth of mouse myeloid M-NFS-60 cells can be observed at 0.7μM by GW2580. Treatment with GW2580 at 1μM inhibited CSF-1-, GMCSF- and LPS-induced human monocytes growth by 100%, 80% and 50%, respectively. This can be also confirmed in vivo as oral dosed mice with GW2580 at 40mg/kg before CSF-1-priming dose completely blocked the ability of MCSF to increase LPS-induced IL-6 production, but slightly increased LPS-induced IL-6 production before vehicle-priming dose. It showed that oral dose with GW2580 at 20 and 80mg/kg, BID, before thioglycolate injection for 4 days could inhibit thioglycolate-induced macrophage Influx into the peritoneal cavity in vivo. Oral administration of GW2580 at 20 and 80mg/kg, BID, at 1h before i.p. injection of M-NFS-60 cells, produced a dose-related decrease in the number of tumor cells in mice on 4 days later[1].
作用机制
GW2580 acts as a competitive inhibitor of ATP binding to the cFMS kinase.[1]
GW2580 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
human BT474 cells
Growth inhibition assay
Growth inhibition of serum-stimulated human BT474 cells after 3 days by spectrophotometry, IC50=21 μM
16249345
human HN5 cells
Growth inhibition assay
Growth inhibition of serum-stimulated human HN5 cells after 3 days by spectrophotometry, IC50=29 μM
16249345
human PBMC
Function assay
Inhibition of LPS-induced IL6 production in human PBMC by ELISA, EC50=1.89 μM
23095041
HUVEC
Growth inhibition assay
Growth inhibition of VEGF-stimulated HUVEC after 3 days by spectrophotometry
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