870483-87-7

GW-2580 (870483-87-7) is a potent and selective inhibitor of cFMS receptor kinase. Completely inhibits cFMS in vitro at 60 nM with no activity against 26 other kinases1. Completely inhibits CSF-1 induced growth of mouse M-NFS-60 myeloid cells and human monocytes (at 1 μM)1. GW-2580 completely inhibits bone degradation in human osteoclasts, rat calvaria and fetal long bone1. Inhibits LPS-induced TNF production in mice. GW-2580 abrogates infiltration of macrophages into synovial joints of arthritic mice2. Active in vivo.

GW2580 is a cell-permeable, potent and selective ATP-competitive inhibitor of cFMS kinase, receptor for macrophage-colony stimulating factor, M-CSF or CSF-1, and a key regulator of macrophage and osteoclast activation and differentiation. FMS is a type III receptor tyrosine kinase that binds to the macrophage or monocyte colony-stimulating factor (M-CSF or CSF-1). Overexpression of CSF-1 and/or FMS has been implicated in a number of disease states including the growth of metastasis of some types of cancer, in promoting osteoclast proliferation in bone osteolysis, and in several inflammatory disorders. GW2580 selectively inhibits cFMS-mediated cellular functions in vitro at 0.06 μM as well as CSF-1-dependent tumor growth in vivo. GW2580 was inactive against 26 other kinases.

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1) Conway et al. (2005), Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580; Proc. Natl. Acad. Sci. USA, 102 16078 2) Paniagua et al. (2010), c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis; Arthritis Res. Ther., 12 R32