Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Fedratinib (TG-101348) 是一种 JAK2 抑制剂,具有选择性、ATP 竞争性和具有口服活性,抑制 JAK2 和 JAK2V617F 激酶 (IC50=3 nM)。Fedratinib 可诱导肿瘤细胞凋亡,并可用于骨髓增生性疾病的研究。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
2 mg | ¥ 265 | 现货 | ||
5 mg | ¥ 379 | 现货 | ||
10 mg | ¥ 543 | 现货 | ||
25 mg | ¥ 773 | 现货 | ||
100 mg | ¥ 1,198 | 现货 | ||
200 mg | ¥ 1,995 | 现货 | ||
500 mg | ¥ 4,280 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 481 | 现货 |
产品描述 | Fedratinib (TG-101348) is a JAK2 inhibitor that is selective, ATP-competitive, and orally active, inhibiting JAK2 and JAK2V617F kinases (IC50=3 nM). Fedratinib induces apoptosis in tumor cells and may be used in myeloproliferative diseases. |
靶点活性 | FLT3:15 nM (cell free), JAK2 (V617F):3 nM (cell free), JAK2:3 nM (cell free), RET:48 nM (cell free) |
体外活性 |
方法:人成红细胞白血病细胞 HEL 和 Ba/F3 JAK2V617F 细胞用 Fedratinib (0-30 µM) 处理 72 h,使用 XTT assay 检测细胞增殖。 结果:Fedratinib 抑制了携带 JAK2V617F 突变的 HEL 细胞系以及表达人 JAK2V617F (Ba/F3 JAK2V617F) 的鼠前 B 细胞系的增殖,两种细胞系的 IC50 值分别为 305 nM 和 270 nM。[1] 方法:人骨髓间充质干细胞 hMSC-TERT 用 Fedratinib (3 µM) 处理 10 天,进行碱性磷酸酶 (ALP) 染色检测成骨分化。 结果:Fedratinib 处理的 hMSC-TERT 细胞表现出 ALP 产生的显著减少。与对照细胞相比,成骨细胞分化诱导后第 10 天的 ALP 活性测量值降低。Fedratinib 对 hMSC-TERT 细胞的活力没有产生显著影响。[2] |
体内活性 |
方法:为研究对已建立的真性红细胞增多症的疗效,将 Fedratinib (60-120 mg/kg) 灌胃给药给 C57BL/6 小鼠骨髓移植模型,每天两次,持续 42 天。 结果:在接受治疗的动物中,红细胞压积和白细胞计数在统计学上显著降低,髓外造血的减少/消除呈剂量依赖性,至少在某些情况下,有证据表明骨髓纤维化减轻。[1] |
激酶实验 | IC50 values for TG101348 are determined commercially using the InVitrogen kinase profiling service for a 223 kinase screen that included JAK2 and JAK2V617F or Carna Biosciences for the screen of all Janus kinase family members including JAK1 and Tyk2. ATP concentration is set to approximately the Km value for each kinase [1]. |
细胞实验 | Cells were treated with DMSO and increasing concentrations of inhibitor for 4 hr in RPMI-1640 before collected in 13 Cell Lysis Buffer, containing 1 mM PMSF, and protease inhibitor cocktail tablets. Protein lysates were quantified with BCA assay. Similar protein amounts were mixed with Laemmli sample buffer plus b-mercaptoethanol, boiled for 5 min, and separated on a 4%–15% Tris-HCl gradient electrophoresis gel. Gels were blotted onto a 0.45 mm nitrocellulose membrane, which was blocked in 5% nonfat dry milk and incubated with primary antibodies in either blocking solution or 5% BSA. The membranes were subsequently incubated with a mixture of donkey anti-rabbit IgG conjugated with infrared fluorophore (700 nm emission) and goat anti-mouse IgG conjugated with infrared fluorophore (800 nm emission). Following washing with PBS, the membranes were scanned on an Odyssey scanner to detect total (red) and phospho-STAT5 (green) proteins [1]. |
动物实验 | The murine BM transplant model was generated and analyzed exactly as previously described. Briefly, C57BL/6 mice were intravenously injected with 1×10^6 whole bone marrow expressing JAK2V617F. Full development of disease was assessed with differential peripheral blood counts at day 26 after bone marrow transplantation. TG101348 was administered by oral gavage twice daily (b.i.d.) at 60 mg/kg, 120 mg/kg, or placebo from day 28 on for 42 days. Differential blood counts were assessed by retro-orbital nonlethal eye bleeds using EDTA glass capillary tubes before study initiation, during the study, and at study endpoints. C57/Bl6 mice were sacrificed at study endpoint or at times indicated based on an IUCAC-approved protocol that includes assessment of morbidity by > 10% loss of weight, scruffy appearance, lethargy, and/or splenomegaly extending across the midline. For histopathology, tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, and stained with hematoxylin and eosin or, to assess for fibrosis, stained with reticulin. Images of histological slides were obtained on a Nikon Eclipse E400 microscope equipped with a SPOT RT color digital camera model 2.1.1. Images were analyzed in Adobe Photoshop 6.0. For flow cytometry, cells were washed in PBS, washed in 2% fetal bovine serum, blocked with Fc-Block for 10 min on ice, and stained with monoclonal antibodies in PBS and 2% FCS for 30 min on ice. Antibodies used were allophycocyanin (APC)-conjugated ter119, Gr-1, CD4, and B220 and phycoerythrin (PE)-conjugated, Mac1, CD8 (all 1:200), and CD71(1:100) rat anti-mouse. After washing, cells were resuspended in PBS and 2% FCS containing 0.5 mg/ml 7-amino-actinomycin D (7-AAD) to allow discrimination of nonviable cells. Flow cytometry was performed on a FACS Calibur cytometer, at least 10,000 events were acquired, and data were analyzed using FloJo software.The results are presented as graphs and representative dot plots of viable cells selected on the basis of scatter and 7-AAD staining [1]. |
别名 | TG-101348, SAR 302503 |
化合物与蛋白结合的复合物 |
JAK2 JH1 in complex with Fedratinib |
分子量 | 524.68 |
分子式 | C27H36N6O3S |
CAS No. | 936091-26-8 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 50 mg/mL (95.3 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.9059 mL | 9.5296 mL | 19.0592 mL | 47.6481 mL |
5 mM | 0.3812 mL | 1.9059 mL | 3.8118 mL | 9.5296 mL | |
10 mM | 0.1906 mL | 0.953 mL | 1.9059 mL | 4.7648 mL | |
20 mM | 0.0953 mL | 0.4765 mL | 0.953 mL | 2.3824 mL | |
50 mM | 0.0381 mL | 0.1906 mL | 0.3812 mL | 0.953 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Fedratinib 936091-26-8 Angiogenesis Apoptosis Chromatin/Epigenetic JAK/STAT signaling Stem Cells Tyrosine Kinase/Adaptors FLT c-RET JAK STAT5 Inhibitor Janus kinase phosphorylation FLT3 myeloproliferative SAR-302503 JAK2V617F orally inhibit SAR302503 anti-proliferation JAK2 TG 101348 TG-101348 TG101348 RET anti-cancer SAR 302503 inhibitor