GW-2580 (GW2580)

Cas No.:	870483-87-7
Chemical Name:	5-(3-Methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine
Synonyms:	5-[3-Methoxy-4-(4-methoxybenzyloxy)benzyl]pyrimidine-2,4-diamine;5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine;GW2580;5-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]pyrimidine-2,4-diamine;cFMS Receptor Tyrosine Kinase Inhibitor;GW-2580;GW2580, FREE BASE;PLX-0728;2,4-Pyrimidinediamine,5-((3-methoxy-4-((4-methoxyphenyl)methoxy)phenyl)methyl);4at5;5-(3-Methoxy-4-((4-methoxybenzyl)oxy)benzyl)-pyrimidine-2,4-diamine;CSF-1 Receptor Inhibitor;Kinome_3757;5-[[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-2,4-Pyrimidinediamine;5-[3-Methoxy-4-[(4-methoxybenzyl)oxy]benzyl]pyrimidine-2,4-diamine;GW 2580;GW632580X;SRV0JCF9LI;5-{3-methoxy-4-[(4-methoxybenzyl)oxy]benzyl}pyrimidine-2,4-diamine;5-(3-Methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine;5-(3-METHOXY-4-(4-METHOXYBENZYLOXY)BENZYL)PYRIMIDINE-2,4-DIAMINE;2,4-Pyrimidinediamine, 5-((3-methoxy-4-((4-methoxyphenyl)methoxy)phenyl)methyl)-;CSF-1 Rece
SMILES:	O(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1OC([H])([H])[H])C([H])([H])C1=C([H])N=C(N([H])[H])N=C1N([H])[H]
Formula:	C20H22N4O3
M.Wt:	366.4137
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	GW2580 is an orally bioavailable inhibitor of c-Fms kinase which completely inhibits human cFMS kinase in vitro at 0.06 μM.
In Vivo:	GW2580 (dosed orally at 40 mg/kg 0.5 h before the CSF-1-priming dose) blocks the ability of exogenous CSF-1 to increase LPS-induced TNF-α production in mice by 63%. When given to mice before CSF-1 priming, GW2580 completely blocks the ability of CSF-1 to prime the mouse for increased IL-6 production. GW2580 (80 mg/kg p.o.) completely inhibits the growth of CSF-1-dependent M-NFS-60 tumor cells in the peritoneal cavity. GW2580 (80 mg/kg) dosed orally twice a day the week before thioglycolate injection and for the 4-day period after thioglycolate injection, diminishes the accumulation of macrophages in the peritoneal cavity after thioglycolate injection (by 45%)[1]. Gw2580 (160 mg/kg) induces a more than 2-fold reduction of total CD45+ CD11b+ myeloid cells, CD11b+ F4/80+ TAMs, and CD11b+ Gr-1+ MDSCs in implanted 3LL lung tumor, through inhibiting tumor recruitment of myeloid cells from peripheral blood. GW2580 (80 mg/kg) treatment is able to suppress Vegf-a (by 35%) and Mmp9 (by 70%) expression, as well as tumor vascular density (CD31 staining). Combination therapy with GW2580 and an anti-VEGFR-2 antibody results in synergistic tumor growth reduction. DC101 alone reduces tumor growth by 35%, the combination of DC101 and GW2580 results in an apparent synergistic tumor growth reduction of approximately 70%[2]. In a 21-day adjuvant arthritis model, GW2580 (50 mg/kg) dosed twice a day from days 0 to 21, 7 to 21, or 14 to 21 inhibits joint connective tissue and bone destruction[3].
In Vitro:	GW2580 completely inhibits human cFMS kinase in vitro at 0.06 μM. GW2580 inhibits the growth of CSF-1 stimulated M-NFS-60 myeloid tumor cells, serum stimulated NSO myeloid tumor cells, CSF-1 stimulated freshly isolated human monocytes, and VEGF stimulated human umbilical vein vascular endothelial cells with IC50 of 0.33, 13.5, 0.47 and 12 μM, respectively. 1 μM GW2580 completely inhibits CSF-1-induced growth of mouse M-NFS-60 myeloid cells and human monocytes and completely inhibits bone degradation in cultures of human osteoclasts, rat calvaria, and rat fetal long bone[1]. GW2580 inhibits CSF1R phosphorylation in RAW264.7 murine macrophages stimulated with 10 ng/mL with IC50 of approximately 10 nM[2]. GW2580 also inhibits TRKA activity with IC50 of 0.88 μM[3].