| 名稱(chēng) | GW2580 |
| 描述 | GW2580 (SC-203877) is a specific, oral-bioavailable CSF-1R inhibitor for c-FMS. |
| 細(xì)胞實(shí)驗(yàn) | One day before the start of the cell growth assay the cells are spun down and placed in a depleted media at 2× 106 cells per ml for 24 h. Depleted medium for M-NSF60 cells lacks MCSF. The next day, GW2580 at 10 mM in DMSO is diluted to 20 μM and 0.2% DMSO in medium containing 10% serum and serially diluted to yield a 10-point concentration curve. The M-NFS-60 cells are resuspended in medium at 0.5× 106 cells/mL with 10% serum and 20 ng/mL mouse MCSF. Cells (50 μL) are added to each well containing inhibitor (50 μL), and, 3 days later, 10 μL of WST-1 reagent is added to each well. After a 4-h incubation, the absorbance is measured at 440 nm and growth calculated as the difference between wells with full medium and wells with depleted medium.(Only for Reference) |
| 激酶實(shí)驗(yàn) | cFMS tyrosine kinase assay: The enzyme is activated by autophosphorylation by incubating 10 μM enzyme, 100 μM ATP, and 5 mM MgCl2 in 50 mM Tris HCL for 90 min at room temperature. Enzyme reactions are performed in a volume of 45 μL, by using round-bottom polystyrene 96-well plates on a Biomek 2000. Compound in 1 μL DMSO or DMSO alone are added to each well containing 30 μL of a 1.5× substrate reaction mix containing 50 mM Mops (3-[N-Morpholino]propanesulfonic acid), pH 7.5, 15 mM MgCl2, 6 μM peptide substrate, biotin-EAIYAPFAKKK-NH2 7.5 mM DTT, 75 mM NaCl, 10 μM ATP, and 0.5 μCi (1 Ci = 37 GBq) [33P-γ] ATP per assay. The reaction is initiated by the addition of 15 μL of diluted enzyme solution, resulting in a final enzyme concentration 20 nM. EDTA is added to control wells for determination of background. The reaction is allowed to proceed for 40 min and stopped by the addition of an equal volume of 0.5% phosphoric acid, and 75 μL is transferred to a 96-well phosphocellulose filter plate that has been prewet with 100 μL of 0.5% phosphoric acid. The plate is filtered on a Millipore filter-plate vacuum manifold and washed three times with the phosphoric acid solution, followed by the addition of 40 μL of scintillation solution. The plates are sealed and counted in a Packard Topcount NXT scintillation counter. |
| 體外活性 | 在佐劑性關(guān)節(jié)炎模型中,GW2580（50 mg/kg ）能夠抑制關(guān)節(jié)結(jié)締組織和骨破壞.在小鼠中,口服 GW2580（40 mg/kg）能夠抑制外源性CSF-1促進(jìn)脂多糖誘導(dǎo)的TNF-α生成的能力.在腹腔內(nèi)CSF-1依賴(lài)性的M-NFS-60腫瘤細(xì)胞模型中,口服 GW2580（80 mg/kg）能夠抑制腫瘤細(xì)胞生長(zhǎng).在移植3LL肺腫瘤模型中,GW2580（160 mg/kg）能夠抑制骨髓細(xì)胞的生長(zhǎng). |
| 體內(nèi)活性 | GW2580能夠抑制多種細(xì)胞的生長(zhǎng),對(duì)于CSF-1刺激的M-NFS-60骨髓瘤細(xì)胞（IC50=0.33 μM）,血清刺激的NSO骨髓瘤細(xì)胞（IC50=13.5 μM）,CSF-1刺激的新鮮分離的人單核細(xì)胞（IC50=0.47 μM）,和血管內(nèi)皮生長(zhǎng)因子刺激的人臍靜脈血管內(nèi)皮細(xì)胞（IC50=12 μM）。對(duì)于TRKA（IC50=0.88 μM）,人類(lèi)CFMS激酶（0.06 μM）GW2580能夠發(fā)揮抑制作用。在RAW264.7小鼠巨噬細(xì)胞中（IC50=10 nM）,GW2580能通過(guò)抑制CSF1R磷酸化發(fā)揮作用。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 15 mg/mL (40.94 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | c-Fms | GW2580 | SC203877 | inhibit | SC 203877 | GW-2580 | CSF1R | CSF-1 receptor | Inhibitor | CSF-1R | colony stimulating factor 1 receptor |
| 相關(guān)產(chǎn)品 | Onatasertib | Cerdulatinib hydrochloride | Sotuletinib | Masitinib | c-Fms-IN-1 | Linifanib | c-Fms-IN-13 | Pexidartinib | PLX5622 | c-Fms-IN-3 | Vimseltinib | Pazopanib Hydrochloride |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 激酶抑制劑庫(kù) | 高選擇性抑制劑庫(kù) | NO PAINS 化合物庫(kù) | 干細(xì)胞分化化合物庫(kù) | 膜蛋白靶向化合物庫(kù) | 口服活性化合物庫(kù) | 酪氨酸激酶分子庫(kù) |