| Identification | Back Directory | [Name]
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine | [CAS]
870483-87-7 | [Synonyms]
GW2580
CS-621
SC-203877
GW2580, >=98%
GW2580,GW-2580
SC-203877/GW2580
GW2580 (SC203877)
GW 2580; GW-2580; GW 2580.
cFMS receptor TK inhibitor
cFMS Receptor Tyrosine Kinase Inhibitor
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine
cFMS Receptor Tyrosine Kinase Inhibitor - CAS 870483-87-7 - Calbiochem
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine USP/EP/BP
5-[[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]pyrimidine-2,4-diamine
5-[[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-2,4-Pyrimidinediamine
2,4-Pyrimidinediamine, 5-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]- | [Molecular Formula]
C20H22N4O3 | [MDL Number]
MFCD12024701 | [MOL File]
870483-87-7.mol | [Molecular Weight]
366.414 |
| Chemical Properties | Back Directory | [Boiling point ]
617.5±65.0 °C(Predicted) | [density ]
1.252±0.06 g/cm3(Predicted) | [storage temp. ]
?20°C | [solubility ]
DMSO: soluble10mg/mL, clear (warmed) | [form ]
powder | [pka]
7.11±0.10(Predicted) | [color ]
white to beige | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months. | [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]
Nc1nc(c(cn1)Cc2cc(c(cc2)OCc3ccc(cc3)OC)OC)N |
| Hazard Information | Back Directory | [Description]
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. | [Uses]
GW2580 has been used to study its effect on paracrine signaling from stretched cardiomyocyte on cardiac fibroblast phenotype. | [Biochem/physiol Actions]
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. | [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[1].
GW2580 (Oral administration; 20 and 80 mg/kg) has gave maximal plasma concentrations of 1.4 and 5.6 μM, respectively[1].
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[3]. | Animal Model: | Female C3H/HEN mice or female CD-1 nude mice weighing 22-26 g[1] | | Dosage: | 20 and 80 mg/kg | | Administration: | Oral administration | | Result: | Produced a dose-related decrease in the number of tumor cells, with the 80 mg/kg dose completely blocking tumor growth.
|
| Animal Model: | Female C3H/HEN mice or female CD-1 nude mice weighing 22-26 g[1] | | Dosage: | 20 and 80 mg/kg (Pharmacokinetic Study) | | Administration: | Oral administration | | Result: | Had gave maximal plasma concentrations of 1.4 and 5.6 μM, respectively. |
| [storage]
Store at -20°C | [References]
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 |
|
|