Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Tandutinib (CT53518) 是一种选择性 FLT3抑制剂,其 IC50为 0.22 μM。它还抑制c-Kit 和PDGFR,其IC50分别为 0.17 μM 和 0.20 μM。它可穿透血脑屏障,用于急性骨髓性白血病。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
25 mg | ¥ 328 | 现货 | ||
50 mg | ¥ 463 | 现货 | ||
100 mg | ¥ 713 | 现货 | ||
200 mg | ¥ 998 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 512 | 现货 |
产品描述 | Tandutinib (CT53518) (MLN518, CT53518), an effective FLT3 antagonist (IC50: 0.22 μM), can also inhibit c-Kit and PDGFR, 15-20 fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR, and KDR. |
靶点活性 | FLT3:0.22 μM |
体外活性 | 在携带表达W51 FLT3-ITD 突变型Ba/F3细胞的小鼠中,Tandutinib(60 mg/kg,2次/天,p.o.)可显著延长寿命, 而在小鼠骨髓移植模型中,其可使死亡率显著降低.Tandutinib(180 mg/kg,2次/天)对正常造血功能有轻微毒性,作用于小鼠时,对FLT3 ITD-阳性的白血病有良好的治疗效果. |
体内活性 | 与星孢菌素不同,Tandutinib对βPDGF,FLT3和c-Kit自磷酸化具有较好的抑制效果(IC50:0.17-0.22 μM), 但几乎不影响EGFR, FGFR, KDR, InsR, Src, Abl, PKC, PKA和 MAPKs。由于对FLT3抑制的特异性,Tandutinib只对FLT3-ITD阳性Molm-14细胞有效,对FLT3-ITD阴性THP-1细胞无效果,处理24和96 h,造成的细胞凋亡分别为51%和78%。与AML的ITD阴性患者相比,Tandutinib优先抑制AML的FLT3 ITD阳性患者体内爆发式的集落生长,但对正常人祖细胞形成集落没有影响。Tandutinib对不依赖IL-3的细胞生长具有抑制作用,同时抑制FLT3-ITD自磷酸化(IC50:10-100 nM)。Tandutinib对含FLT3-ITD突变的人白血病Ba/F3细胞增殖也有抑制作用(IC50:10-30 nM),还抑制FLT3-ITD-阳性的Molm-13和14细胞(IC50:10 nM)。 |
激酶实验 | Cell based receptor autophosphorylation assays: Autophosphorylation of PDGFR family kinase assays are cell-based enzyme-linked immunosorbent (ELISA) assays using CHO cells expressing wild-type PDGFRβ, chimeric protein PDGFRβ/c-Kit, and PDGFRβ/Flt3 which contain the extracellular and transmembrane domains of PDGFRβ and the cytoplasmic domain of c-Kit, and Flt-3. Cells are grown to confluency in 96-well microtiter plates under standard tissue culture conditions, followed by serum starvation for 16 hours. Briefly, quiescent cells are incubated at 37 °C with increasing concentrations of Tandutinib for 30 minutes followed by the addition of 8 nM PDGF-BB for 10 minutes. Cells are lysed in 100 mM Tris, pH 7.5, 750 mM NaCl, 0.5% Triton X-100, 10 mM sodium pyrophosphate, 50 mM NaF, 10 μg/mL aprotinin, 10 μg/mL leupeptin, 1 mM phenylmethylsulfonyl fluoride, 1 mM sodium vanadate, and the lysate is cleared by centrifugation at 15,000 g for 5 minutes. Clarified lysates are transferred into a second microtiter plate in which the wells are previously coated with 500 ng/well of 1B5B11 anti-PDGFRβ mAb and then incubated for 2 hours at room temperature. After washing three times with binding buffer (0.3% gelatin, 25 mM HEPES, pH 7.5, 100 mM NaCl, 0.01% Tween 20), 250 ng/mL of rabbit polyclonal anti-phosphotyrosine antibody is added and plates are incubated at 37 °C for 60 minutes. Subsequently, each well is washed three times with binding buffer and incubated with 1 μg/mL of horseradish peroxidase-conjugated anti-rabbit antibody at 37 °C for 60 minutes. Wells are washed prior to adding 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and the rate of substrate formation is monitored at 650 nm. |
细胞实验 | Cells are exposed to increasing concentrations of Tandutinib (0.004-30 μM). Cells are grown for 3-7 days in tissue culture, and viable cells, determined by Trypan blue dye exclusion, are counted. At daily intervals, cells are harvested, washed, and resuspended in 100 uL binding buffer containing 10 mM HEPES (pH 7.4), 140 mM NaCl, and 2.5 mM CaCl2. Annexin V-FITC (100 ng) and propidium iodide (250 ng) are added to the cell suspension followed by incubation at room temperature for 15 minutes. Flow cytometry is performed immediately after staining on a FACSort flow cytometer with excitation at 488 nm. Fluorescence of annexin V-FITC and DNA propidium iodide staining are measured at 515 nm and 585 nm, respectively.(Only for Reference) |
别名 | MLN518, CT53518, NSC726292, 坦度替尼 |
分子量 | 562.7 |
分子式 | C31H42N6O4 |
CAS No. | 387867-13-2 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 6 mg/mL (10.66 mM)
DMSO: 10 mg/mL (17.77 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
Ethanol / DMSO | 1 mM | 1.7771 mL | 8.8857 mL | 17.7715 mL | 44.4286 mL |
5 mM | 0.3554 mL | 1.7771 mL | 3.5543 mL | 8.8857 mL | |
10 mM | 0.1777 mL | 0.8886 mL | 1.7771 mL | 4.4429 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。
Tandutinib 387867-13-2 Angiogenesis Apoptosis Tyrosine Kinase/Adaptors FLT CSF-1R PDGFR Src c-Kit CT-53518 Acute MLN 518 FLT3-ITD Inhibitor NSC 726292 inhibit MLN518 autophosphorylation CD135 CT 53518 blood-brain MLN-518 FLT3 myelogenous leukemia Fms like tyrosine kinase 3 MAP barrier CT53518 SCFR Platelet-derived growth factor receptor NSC726292 CD117 Cluster of differentiation antigen 135 坦度替尼 NSC-726292 PI3 inhibitor