Tandutinib (MLN518) 是一种有效和选择性的FLT3的抑制剂,其IC50为 0.22 μM,并且还抑制c-Kit和PDGFR,其IC50分别为 0.17 μM 和 0.20 μM。Tandutinib 可用于急性骨髓性白血病,并具有穿越血脑屏障的能力。
生物活性 | Tandutinib (MLN518) is a potent and selective inhibitor of theFLT3with anIC50of 0.22 μM, and also inhibitsc-KitandPDGFRwithIC50s of 0.17 μM and 0.20 μM, respectively. Tandutinib can be used for acute myelogenous leukemia (AML)[1][2]. Tandutinib has the ability to cross the blood-brain barrier[3]. |
IC50& Target | PDGFR 0.2 μM (IC50) | FLT3 0.22 μM (IC50) | c-Kit 0.17 μM (IC50) |
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体外研究 (In Vitro) | Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with anIC50of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants[1]. Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells[1]. In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC50of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib[1]. Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with anIC50of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways[1].
Apoptosis Analysis[1] Cell Line: | Molm-14 and THP-1 AML cells | Concentration: | 1 μM | Incubation Time: | 24 hours, 48 hours, 72 hours, 96 hours | Result: | Induced apoptosis in FLT3-ITD-positive AML cells. |
Western Blot Analysis[1] Cell Line: | Ba/F3 cells | Concentration: | 0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM | Incubation Time: | 30 minutes | Result: | In Ba/F3 cells expressing different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation. |
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体内研究 (In Vivo) | Tandutinib (60 mg/kg; oral gavage; daily; for 35 days; athymic nude mice) treatment causes a statistically significant increase in survival that was extended on average by 20 days[1].
Animal Model: | Athymic nude mice injected with Ba/F3 cells[1] | Dosage: | 60 mg/kg | Administration: | Oral gavage; daily; for 35 days | Result: | Caused a statistically significant increase in survival that was extended on average by 20 days. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 50 mg/mL(88.86 mM;Need ultrasonic) 配制储备液 1 mM | 1.7771 mL | 8.8857 mL | 17.7715 mL | 5 mM | 0.3554 mL | 1.7771 mL | 3.5543 mL | 10 mM | 0.1777 mL | 0.8886 mL | 1.7771 mL |
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此方案可获得 ≥ 2.5 mg/mL (4.44 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.44 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.44 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (4.44 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.44 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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