| 名稱 | Glumetinib |
| 描述 | Glumetinib (SCC244) is a novel potent and selective inhibitor of c-Met kinase (IC50: 0.42 nM). |
| 細(xì)胞實(shí)驗(yàn) | 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(shí)驗(yàn) | 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(shí)驗(yàn) | 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(yuǎn)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(qiáng)烈抑制了HGF誘導(dǎo)的NCI-H441細(xì)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(xì)胞的移動，顯示出劑量依賴性的作用。 |
| 體內(nèi)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(jìn)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(jié)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(zhì)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(dāng)。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 4.6 mg/mL (10.01 mM), Sonication is recommended.
|
| 關(guān)鍵字 | tumor | SCC-244 | SCC 244 | proliferation | oral | NSCLC | Inhibitor | inhibit | HGFR | HCC | Glumetinib | c-Met/HGFR | cMet/HGFR | c-Met | cMet | cell | cancer | bioavailable | ATP-competitive |
| 相關(guān)產(chǎn)品 | Cabozantinib S-malate | Crizotinib | Tepotinib | (Z)-Semaxinib | Afatinib | Afatinib Dimaleate | Capmatinib | Decanoic Acid | L-Ascorbic acid 2-phosphate trisodium | 7-Methoxy-1-tetralone | Bacitracin Zinc | (S)-Afatinib |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 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 | NO PAINS 化合物庫 | 膜蛋白靶向化合物庫 | 藥物功能重定位化合物庫 | 酪氨酸激酶分子庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |