Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H22N4O3 |
| Molecular Weight | 366.4137 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(COC2=CC=C(CC3=CN=C(N)N=C3N)C=C2OC)C=C1
InChI
InChIKey=MYQAUKPBNJWPIE-UHFFFAOYSA-N
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)
| Molecular Formula | C20H22N4O3 |
| Molecular Weight | 366.4137 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
GW2580 is selective, small molecule tyrosine kinase, cFMS kinase, inhibitor. cFMS kinase is the cellular homolog of the v-FMS oncogene product of the Susan McDonough strain of the feline sarcoma virus. It can autophosphorylate colony-stimulating factor (CSF-1), which promotes the survival, proliferation, and differentiation of mononuclear phagocytes. GW2580 was inactive against 26 other kinases. It has been shown to inhibit joint connective tissue and bone degradation in mouse models of arthritis. In addition, was shown, that GW2580 had potential as novel therapeutic for the treatment of autoimmune demyelinating disease, it could prevent the development of disease and treat established disease in a mouse model of multiple sclerosis. The amelioration of disease by GW2580 was associated with a reduction in the proportion of macrophages and T cells in the CNS infiltrate, as well as a reduction in the levels of circulating TNF.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P07333 Gene ID: 1436.0 Gene Symbol: CSF1R Target Organism: Homo sapiens (Human) |
0.03 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Preventing | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer's-like pathology. | 2016-03 |
|
| A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. | 2013-04-15 |
|
| Regulation of microglial proliferation during chronic neurodegeneration. | 2013-02-06 |
|
| Comprehensive analysis of kinase inhibitor selectivity. | 2011-10-30 |
|
| Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. | 2011-10-30 |
|
| Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood. | 2010-12 |
|
| Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010-11-24 |
|
| Interleukin-34 is expressed by giant cell tumours of bone and plays a key role in RANKL-induced osteoclastogenesis. | 2010-05 |
|
| Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. | 2010-02-18 |
|
| c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis. | 2010 |
|
| Effects of the cFMS kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) in normal and arthritic rats. | 2008-07 |
|
| Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. | 2005-11-01 |
Patents
Sample Use Guides
in rats: 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.
Route of Administration:
Oral
GW2580 completely inhibited human cFMS kinase in vitro at 0.06 μM and was 150- to 500-fold selective compared to human (bRAF, CDK4, cKIT, cSRC, EGFR, ERBB2, ERBB4, ERK2, FLT-3, GSK3, ITK, JAK2, JNK3, MK2, P38, PDGFR-b, PDHK4, PKA, PLK1, PKCα, PKCβ1, PKCζ, SYK, TIE2, and VEGFR2) and mouse (LCK) kinases. GW2580 completely inhibited the growth of CSF-1-dependent mouse myeloid M-NFS-60 cells at 0.7 μM. In contrast, the growth of mouse myeloid NS0 cells, a CSF-1-independent cell line, was highly resistant to GW2580. In freshly isolated human monocytes, GW2580 at 1 μM maximally inhibited CSF-1-, granulocyte-macrophage-stimulating factor (GMCSF) - and LPS-induced growth by 100%, 80%, and 50%, respectively. In contrast to monocytes, the growth of human foreskin fibroblasts, endothelial cells, and five tumor cell lines was highly resistant to GW2580.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:05:08 GMT 2025
by
admin
on
Mon Mar 31 22:05:08 GMT 2025
|
| Record UNII |
SRV0JCF9LI
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Preferred Name | English | ||
|
Common Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
SRV0JCF9LI
Created by
admin on Mon Mar 31 22:05:08 GMT 2025 , Edited by admin on Mon Mar 31 22:05:08 GMT 2025
|
PRIMARY | |||
|
11617559
Created by
admin on Mon Mar 31 22:05:08 GMT 2025 , Edited by admin on Mon Mar 31 22:05:08 GMT 2025
|
PRIMARY | |||
|
870483-87-7
Created by
admin on Mon Mar 31 22:05:08 GMT 2025 , Edited by admin on Mon Mar 31 22:05:08 GMT 2025
|
PRIMARY | |||
|
DTXSID10236095
Created by
admin on Mon Mar 31 22:05:08 GMT 2025 , Edited by admin on Mon Mar 31 22:05:08 GMT 2025
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |
