| 名稱 | TG101209 |
| 描述 | TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM. |
| 細胞實驗 | In brief, approximately 2 × 103 cells are plated into microtiterplate wells in 100 ml RPMI-1640 growth media with indicated concentrations of TG101209. The relative growth of cells is quantified at 24-hour intervals using Cell Proliferation Kit II (XTT) as per manufacturer's guidelines. After incubation, 20 mL of XTT is added to the wells and allowed to incubate for 4-6 hours. The colored formazan product is measured spectrophotometrically at 450 nm with correction at 650 nm, and IC50 values are determined using the GraphPad Prism 4.0 software. Data are subjected to a non-linear regression-fit analysis and IC50 values are determined as the concentration that inhibited proliferation by 50%. All experiments are done in triplicate and the results normalized to growth of untreated cells.(Only for Reference) |
| 激酶實驗 | Cell-free Kinase Activity Assays: IC50 values for TG101209 are determined using a luminescence-based kinase assay with recombinant JAK2, VEGFR2/KDR, and JAK3 obtained from Upstate Cell Signaling Solutions. Kinase reactions are carried out in a buffer consisting of 40 mM Tris buffer (pH 7.4), 50 mM MgCl2, 800?M EGTA, 350?M Triton X-100, 2?M ?-mercaptoethanol, 100?M peptide substrate, and an appropriate amount of JAK2, VEGFR2/KDR or JAK3 such that the assay is linear over 60 minutes. The reaction is initiated by the addition of 10?L of ATP to a final concentration of 3 mM and terminated by the addition of Kinase-Glo reagent after 60 minutes. Luciferase activity is quantified using an Ultra 384 instrument set for luminosity measurements. IC50 values are derived from experimental data using the non-linear curve fitting capabilities of the GraphPad Prism 4.0 software. The single concentration inhibition data for a panel of 63 kinases is determined using the SelectScreen TM service. |
| 體外活性 | 與安慰劑處理的動物相比,TG101209處理的動物體內(nèi)循環(huán)腫瘤細胞負荷顯著減少,呈劑量依賴性,在+11天時減少比例達到20%.100 mg/kg TG101209有效延長JAK2V617F誘發(fā)的患病動物的存活時間（10天）. |
| 體內(nèi)活性 | TG101209抑制HCC2429和H460肺癌細胞中存活素,并降低STAT3的磷酸化作用。TG101209在表達人JAK2V617F的急性髓細胞性白血病細胞系中,誘導細胞周期阻滯和細胞凋亡,并抑制JAK2V617F,STAT5和STAT3的磷酸化。TG101209抑制表達JAK2V617F或MPLW515L突變體的Ba/F3細胞生長,IC50為B200 nM。TG101209抑制來自攜帶JAK2V617F或MPL515突變的原始祖細胞的造血集落的生長。TG101209明顯減少STAT5磷酸化,而不影響STAT5蛋白質(zhì)的總量。TG101209消除BCR-JAK2和STAT5的磷酸化,減少Bcl-xL表達,并引發(fā)轉(zhuǎn)化的Ba/F3細胞凋亡。 |
| 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 : 94 mg/mL (184.43 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關鍵字 | TG-101209 | TG101209 | TG 101209 | RET | Janus kinase | JAK3 | JAK2 | JAK | Inhibitor | inhibit | Fms like tyrosine kinase 3 | FLT3 | cRET | Cluster of differentiation antigen 135 | CD135 | Autophagy | Apoptosis |
| 相關產(chǎn)品 | Naringin | Guanidine hydrochloride | L-Glutamic acid | Gefitinib | Cysteamine hydrochloride | Alginic acid | Hydroxychloroquine | Stavudine | Dextran sulfate sodium salt (MW 4500-5500) | L-Ascorbic acid sodium salt | Paeonol | Sodium 4-phenylbutyrate |
| 相關庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗胰腺癌化合物庫 | 激酶抑制劑庫 | 抗糖尿病庫 | JAK-STAT 化合物庫 | 抗衰老化合物庫 | 抗肝癌化合物庫 | 免疫/炎癥分子化合物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 |