GW2580

A potent, selective c-Fms (CSF1R) inhibitor that completely inhibits human cFMS kinase in vitro at 60 nM; 150- to 500-fold selective compared to 26 other kinases (cKIT, cSRC, EGFR, etc.) ; completely inhibits the growth of CSF-1-dependent mouse myeloid M-NFS-60 cells at 0.7 uM; inhibits LPS-induced TNF production in mice and orally bioavailable. (In Vitro) :GW2580 completely inhibits the growth of CSF-1-dependent mouse myeloid M-NFS-60 cells at 0.7 μM. GW2580 at 0.8-1 μM completely blocks the ability of CSF-1 to induce the growth of mouse M-NFS60 myeloid cells and human monocytes.GW2580 causes a 30-40% inhibition of PTH-induced calcium release at 0.1-0.3 μM, with higher concentrations of 1, 3, and 10 μM completely inhibiting the PTH response.GW2580 inhibits CSF1R phosphorylation in RAW264.7 murine macrophages stimulated with 10 ng/mL with IC50 of approximately 10 nM.GW2580 also inhibits TRKA activity with IC50 of 0.88 μM. (In Vivo) :GW2580 (Oral administration; 20 and 80 mg/kg) produces a dose-related decrease in the number of tumor cells, with the 80 mg/kg dose completely blocking tumor growth.GW2580 (Oral administration; 20 and 80 mg/kg) has gave maximal plasma concentrations of 1.4 and 5.6 μM, respectively.GW2580 (50 mg/kg; twice a day from days 0 to 21, 7 to 21, or 14 to 21) inhibits joint connective tissue and bone destruction in a 21-day adjuvant arthritis model.