GW2580
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MedKoo CAT#: 401482

CAS#: 870483-87-7

Description: GW2580 is an orally bioavailable inhibitor of cFMS kinase. GW2580 was found to completely inhibit human cFMS kinase in vitro at 0.06 microM and was inactive against 26 other kinases. 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. 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.

Chemical Structure

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GW2580
CAS# 870483-87-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 401482
Name: GW2580
CAS#: 870483-87-7
Chemical Formula: C20H22N4O3
Exact Mass: 366.17
Molecular Weight: 366.410
Elemental Analysis: C, 65.56; H, 6.05; N, 15.29; O, 13.10

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 225 Ready to ship
100mg USD 385 Ready to ship
200mg USD 650 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
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Synonym: GW 2580; GW-2580; GW 2580.

IUPAC/Chemical Name: 5-(3-Methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine

InChi Key: MYQAUKPBNJWPIE-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: NC1=NC=C(CC2=CC=C(OCC3=CC=C(OC)C=C3)C(OC)=C2)C(N)=N1

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:         

Biological target: GW2580 is an inhibitor of c-Fms kinase which completely inhibits human cFMS kinase in vitro at 0.06 μM.
In vitro activity: In order to determine whether the cell death was associated with the anti-proliferation effects of CSF-1 antagonism this study examined cell health using the ApoTox-Glo triplex assay. Interestingly while 20 µM GW2580 reduced SW.71 proliferation and also could block the proliferative effects of exogenous CSF-1 it was not associated with a reduction in cell viability (Fig. 2D). However, at the 40 µM dose there was a reduction in viability in the absence (p < 0.05) and presence (p < 0.01) of exogenous CSF-1 (Fig. 2D). There was increased cytotoxicity with 40 µM GW2580 (p < 0.05) and this was not overcome by the addition of CSF-1 (p < 0.05; Fig. 2E). CSF-1 promotes cell survival in immortalised first trimester trophoblast cells. Reference: Sci Rep. 2020; 10: 15638. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519033/
In vivo activity: GW2580 completely blocked the MPTP-induced gene expression of Iba1 in the mouse striatum, along with significant reduction of Iba1+ and Ki-67+/ Iba1+ cells in the SN (Figure 4). This was accompanied by reduced levels of phosphorylated CSF1R, without a significant reduction of the basal microglial population, indicating that GW2580 primarily blocks the activation of CSF1R. The discrepancies among the different inhibitors are likely related to the dose and treatment duration. For instance, BLZ945 is highly specific for CSF1R with an IC50 about 1nM, but can also inhibit c-kit (3.2μM) and PDGFR-β (4.8μM) at higher concentrations. Similarly, GW2580 has an IC50 for CSF1R around 10 nM, but can also inhibit TRKA around 88 nM. Therefore, activity for related kinases along with dose of CSF1R inhibitors appears to be an important factor in determining significant off-target or enhanced target-mediated effects and could explain variation in experimental results between studies. Reference: FASEB J. 2020 Jan; 34(1): 1679–1694. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212500/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 10.0 27.29

Preparing Stock Solutions

The following data is based on the product molecular weight 366.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ahmad SF, Duncan WC, Campbell LL, Beaty RE, Koscielniak M, Collins F, Saunders PTK, Horne AW. Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy. Sci Rep. 2020 Sep 24;10(1):15638. doi: 10.1038/s41598-020-72785-y. PMID: 32973322; PMCID: PMC7519033. 2. Edwards DK 5th, Watanabe-Smith K, Rofelty A, Damnernsawad A, Laderas T, Lamble A, Lind EF, Kaempf A, Mori M, Rosenberg M, d'Almeida A, Long N, Agarwal A, Sweeney DT, Loriaux M, McWeeney SK, Tyner JW. CSF1R inhibitors exhibit antitumor activity in acute myeloid leukemia by blocking paracrine signals from support cells. Blood. 2019 Feb 7;133(6):588-599. doi: 10.1182/blood-2018-03-838946. Epub 2018 Nov 13. PMID: 30425048; PMCID: PMC6367650. 3. Neal ML, Fleming SM, Budge KM, Boyle AM, Kim C, Alam G, Beier EE, Wu LJ, Richardson JR. Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration. FASEB J. 2020 Jan;34(1):1679-1694. doi: 10.1096/fj.201900567RR. Epub 2019 Dec 4. PMID: 31914683; PMCID: PMC7212500. 4. Gerber YN, Saint-Martin GP, Bringuier CM, Bartolami S, Goze-Bac C, Noristani HN, Perrin FE. CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury. Front Cell Neurosci. 2018 Oct 16;12:368. doi: 10.3389/fncel.2018.00368. PMID: 30386212; PMCID: PMC6198221.
In vitro protocol: 1. Ahmad SF, Duncan WC, Campbell LL, Beaty RE, Koscielniak M, Collins F, Saunders PTK, Horne AW. Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy. Sci Rep. 2020 Sep 24;10(1):15638. doi: 10.1038/s41598-020-72785-y. PMID: 32973322; PMCID: PMC7519033. 2. Edwards DK 5th, Watanabe-Smith K, Rofelty A, Damnernsawad A, Laderas T, Lamble A, Lind EF, Kaempf A, Mori M, Rosenberg M, d'Almeida A, Long N, Agarwal A, Sweeney DT, Loriaux M, McWeeney SK, Tyner JW. CSF1R inhibitors exhibit antitumor activity in acute myeloid leukemia by blocking paracrine signals from support cells. Blood. 2019 Feb 7;133(6):588-599. doi: 10.1182/blood-2018-03-838946. Epub 2018 Nov 13. PMID: 30425048; PMCID: PMC6367650.
In vivo protocol: 1. Neal ML, Fleming SM, Budge KM, Boyle AM, Kim C, Alam G, Beier EE, Wu LJ, Richardson JR. Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration. FASEB J. 2020 Jan;34(1):1679-1694. doi: 10.1096/fj.201900567RR. Epub 2019 Dec 4. PMID: 31914683; PMCID: PMC7212500. 2. Gerber YN, Saint-Martin GP, Bringuier CM, Bartolami S, Goze-Bac C, Noristani HN, Perrin FE. CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury. Front Cell Neurosci. 2018 Oct 16;12:368. doi: 10.3389/fncel.2018.00368. PMID: 30386212; PMCID: PMC6198221.

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