| 名稱 | Glumetinib |
| 描述 | Glumetinib (SCC244) is a novel potent and selective inhibitor of c-Met kinase (IC50: 0.42 nM). |
| 細胞實驗 | Cells were seeded in 96-well plates at a low density in growth media. The next day, appropriate controls or designated concentrations of compounds were added to each well, and the cells were incubated for 72 hours. HUVECs (passage 3) were seeded in 96-well plates in growth media overnight and transferred to serum-free media for 24 hours. The following day, appropriate controls or designated concentrations of compounds were added to each well, and HGF was added to designated wells at 100 ng/mL. The cells were incubated for 48 hours. Finally, cell proliferation was determined using a sulforhodamine B assay, a thiazolyl blue tetrazolium bromide assay or a cell counting kit (CCK-8) assay. |
| 激酶實驗 | Met, Ron, Axl, TyrO3, and Mer kinases activity were assessed using both ELISA and radiometric protein kinase assays. The kinase selectivity profile of SCC244 (1 μmol/L) was screened against a panel of other 308 recombinant kinases using radiometric protein kinase assays was also performed according to the manufacturer's specifications. |
| 動物實驗 | To assess the pharmacodynamics of SCC244 in tumors, mice bearing established xenograft tumors were treated with a single dose of the compound at 10 or 2.5 mg/kg, and tumors were harvested at several time points. At a designated time following administration, mice were humanely euthanized, and their tumors were resected. The tumors were snap-frozen in liquid nitrogen and then homogenized in 500 μL of protein extraction solution (radioimmunoprecipitation assay, RIPA). The tumor extracts were then subjected to Western blot analysis. The individual bands of phospho-c-Met, phospho-AKT, and phospho-ERK were scanned and quantified using Gel Pro Analyzer software. The relative tyrosine phosphorylation of each sample at the indicated time points was then calculated, with the average value of vehicle-treated sample used as 100%. |
| 體外活性 | Glumetinib在使用ELISA激酶測定法對純化的c-Met激酶活性表現(xiàn)出高效能(IC50: 0.42 nM)。Glumetinib對c-Met的選擇性超過了2,400倍，遠高于所評估的312種激酶，包括c-Met家族成員RON以及與之高度同源的激酶Axl、Mer和TyrO3。Glumetinib強烈抑制了HGF誘導的NCI-H441細胞的遷移和侵襲能力，并且在10 nmol/L的劑量下足以阻止大多數(shù)細胞的移動，顯示出劑量依賴性的作用。 |
| 體內活性 | 在MKN-45模型中，Glumetinib以10、5和2.5 mg/kg的劑量分別顯著抑制腫瘤生長，抑制率分別為99.3%、88.6%和63.6%。此外，在使用5和10 mg/kg劑量的Glumetinib進行21天治療后，觀察到腫瘤停滯。在SNU-5模型中使用Glumetinib治療得到了類似結果，并且在高劑量組中觀察到腫瘤回歸。在EBC-1研究中，所有接受Glumetinib治療的小鼠，其腫瘤質量均減少了超過66.0%，且在10和5 mg/kg治療組中，每6只小鼠中就有1只未發(fā)現(xiàn)腫瘤。此外，在所有測試模型中，Glumetinib在10 mg/kg的效力與INCB28060在15 mg/kg和crizotinib在50 mg/kg的效力相當。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 4.59 mg/mL (10 mM), Sonication is recommended.
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| 關鍵字 | Glumetinib | proliferation | tumor | cancer | bioavailable | oral | HCC | inhibit | c-Met/HGFR | SCC-244 | ATP-competitive | cell | NSCLC | Inhibitor | SCC 244 |
| 相關產(chǎn)品 | Capmatinib 2HCl | Cabozantinib S-malate | Crizotinib | Amuvatinib | BMS 777607 | (±)-Norcantharidin | Capmatinib xHCl | LMTK3-IN-1 | L-Ascorbic acid 2-phosphate trisodium | Norcantharidin | Bacitracin Zinc | AMG-458 |
| 相關庫 | 抑制劑庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 高選擇性抑制劑庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |