GW2580

• CAT Number: I005240
• CAS Number: 870483-87-7
• Molecular Formula: C₂₀H₂₂N₄O₃
• Molecular Weight: 366.41
• Purity: ≥95%
• Synonyms: 5-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]pyrimidine-2,4-diamine
• Target: CSF-1R
• Solubility: DMSO: ≤ 17.5 mg/mL
• Storage: 3 years -20C powder
• IC50: 60 nM (100% inhibition in vitro) [1]
• InChI: InChI=1S/C20H22N4O3/c1-25-16-6-3-13(4-7-16)12-27-17-8-5-14(10-18(17)26-2)9-15-11-23-20(22)24-19(15)21/h3-8,10-11H,9,12H2,1-2H3,(H4,21,22,23,24)
• InChIKey: MYQAUKPBNJWPIE-UHFFFAOYSA-N
• SMILES: COC1=CC=C(C=C1)COC2=C(C=C(C=C2)CC3=CN=C(N=C3N)N)OC

GW2580 is an orally bioavailable inhibitor of c-FMS kinase; completely inhibited human cFMS kinase in vitro at 0.06 microM and was inactive against 26 other kinases.IC50 value: 60 nM (100% inhibition in vitro) [1]Target: c-Fms kinase inhibitorin vitro: 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 [1]. 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 [2].in vivo: 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 [1]. 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 [2].

Reference

1:Effects of the cFMS kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) in normal and arthritic rats. Conway JG, Pink H, Bergquist ML, Han B, Depee S, Tadepalli S, Lin P, Crumrine RC, Binz J, Clark RL, Selph JL, Stimpson SA, Hutchins JT, Chamberlain SD, Brodie TA.J Pharmacol Exp Ther. 2008 Jul;326(1):41-50. doi: 10.1124/jpet.107.129429. Epub 2008 Apr 23. PMID: 18434589 Free Article2:Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Conway JG, McDonald B, Parham J, Keith B, Rusnak DW, Shaw E, Jansen M, Lin P, Payne A, Crosby RM, Johnson JH, Frick L, Lin MH, Depee S, Tadepalli S, Votta B, James I, Fuller K, Chambers TJ, Kull FC, Chamberlain SD, Hutchins JT.Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16078-83. Epub 2005 Oct 25. PMID: 16249345 Free PMC Article