GW2580 |
Catalog No.GC17286
One-Click Copy Product Info
|
GW2580 is a selective and orally bioavailable inhibitor of colony-stimulating factor-1 receptor (CSF-1R), with an IC50 of 30nM, and completely inhibits the human c-Fms kinase at 0.06μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 870483-87-7
Sample solution is provided at 25 µL, 10mM.
GW2580 is a selective and orally bioavailable inhibitor of colony-stimulating factor-1 receptor (CSF-1R), with an IC50 of 30nM, and completely inhibits the human c-Fms kinase at 0.06μM [1]. CSF-1R (c-Fms) is a receptor tyrosine kinase of the platelet-derived growth factor receptor family, playing a crucial role in hematopoiesis, regulating proliferation, the cell survival and maturation of microglia and monocytes, and controlling the overall immune response [2]. GW2580 has been proven to inhibit the CSF-1R signaling in epithelial cells, reduce the expansion of myeloid cells (MDSCs), and alleviate the immunosuppressive microenvironment [3-4].
In vitro, GW2580 (10, 100, and 1000nM; 6; 24, 48, and 72h) dose-dependently inhibited the cell viability of mouse bone marrow-derived macrophages (BMDMs) stimulated by colony-stimulating factor-1 (CSF-1), with an IC50 of approximately 100nM [5]. GW2580 (0-5μM; 48h) treatment significantly inhibited the expression of Ndufs8, Prdx2, Prdx5, and Gpx4 in primary mouse microglia stimulated by CSF1, without affecting cell viability [6].
In vivo, after GW2580 treatment (60mg/kg/day for 14 days; oral gavage), the total CD45+CD11b+ myeloid cells in the tumors of mice subcutaneously implanted with 3LL tumor cells decreased by more than two-fold, and CD11b+F4/80+TAM also decreased by more than two-fold [5]. GW2580 (0.1% diet, 150mg/kg/day; 1 week) treatment could improve the motor function of spinal cord injury (SCI) mice, inhibit the proliferation of mouse microglia, regulate the neuroglial reactivity, and increase the density of intact myelin fibers in the tail lesion [7].
References:
[1] Conway JG, McDonald B, Parham J, et al. Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A. 2005;102(44):16078-16083.
[2] Hume D A, MacDonald K P A. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling[J]. Blood, The Journal of the American Society of Hematology, 2012, 119(8): 1810-1820.
[3] Fermi V, Warta R, Wöllner A, et al. Effective reprogramming of patient-derived M2-polarized glioblastoma-associated microglia/macrophages by treatment with GW2580[J]. Clinical Cancer Research, 2023, 29(22): 4685-4697.
[4] Kuhn S, Yang J, Ronchese F. Monocyte-derived dendritic cells are essential for CD8+ T cell activation and antitumor responses after local immunotherapy[J]. Frontiers in immunology, 2015, 6: 584.
[5] Priceman SJ, Sung JL, Shaposhnik Z, et al. Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood. 2010;115(7):1461-1471.
[6] Soto-Diaz K, Vailati-Riboni M, Louie AY, McKim DB, Gaskins HR, Johnson RW, Steelman AJ. Treatment With the CSF1R Antagonist GW2580, Sensitizes Microglia to Reactive Oxygen Species. Front Immunol. 2021 Nov 26;12:734349.
[7] Poulen G, Aloy E, Bringuier C M, et al. Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates[J]. Theranostics, 2021, 11(18): 8640.
| Cell experiment [1]: | |
Cell lines | BMDMs cells |
Preparation Method | Cell viability studies were performed using murine bone marrow–derived macrophages (BMDMs). Briefly, mouse bone marrow cells were harvested by flushing the tibias and femurs of adult C57BL/6 mice followed by red blood cell (RBC) lysis. Cells were cultured for 5 to 7 days in complete DMEM with 10ng/mL mouse CSF-1. BMDMs (1.5 × 104 cells/well in 96-well plates) were incubated with 10 or 50ng/mL CSF-1 in the presence or absence of GW2580. GW2580 was dissolved in dimethyl sulfoxide at 25mM and stored at −20°C. Cell viability was measured at indicated time points using the CCK-8 assay. |
Reaction Conditions | 10, 100, and 1000nM; 6; 24, 48, and 72h |
Applications | The GW2580 dose-dependently inhibited the cell viability of BMDMs stimulated by CSF-1, with an IC50 value of approximately 100nM. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | 3LL cells (2 × 105 cells) and B16F1 cells (105 cells) were implanted subcutaneously above the right shoulder of C57BL/6 male mice. Mice were treated with control diluent (0.5% hydroxypropyl methylcellulose; 0.1% Tween20 in distilled H2O) or GW2580 by oral gavage beginning 1 day after tumor implantation. Mice were treated with 160mg/kg GW2580 daily by oral gavage. Tumor size was measured by digital calipers as previously described. Mice were killed and tissues were analyzed using flow cytometry at the ethical tumor size limit of 1cm in diameter. |
Dosage form | 60mg/kg/day for 14 days; oral gavage. |
Applications | After treatment with GW2580, the total number of CD45+CD11b+ myeloid cells in the tumors of mice with 3LL tumor cells was reduced by more than twice, and the number of CD11b+F4/80+TAM also decreased by more than twice. |
References: | |
| Cas No. | 870483-87-7 | SDF | |
| Chemical Name | 5-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]pyrimidine-2,4-diamine | ||
| Canonical SMILES | COC1=CC=C(C=C1)COC2=C(C=C(C=C2)CC3=CN=C(N=C3N)N)OC | ||
| Formula | C20H22N4O3 | M.Wt | 366.41 |
| Solubility | ≥ 36.6mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.7292 mL | 13.6459 mL | 27.2918 mL |
| 5 mM | 545.8 μL | 2.7292 mL | 5.4584 mL |
| 10 mM | 272.9 μL | 1.3646 mL | 2.7292 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)