Tandutinib hydrochloride (MLN518 hydrochloride) 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 hydrochloride 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 hydrochloride (MLN518 hydrochloride) 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 hydrochloride can be used for acute myelogenous leukemia (AML)[1][2]. Tandutinib hydrochloride has the ability to cross the blood-brain barrier[3]. |
IC50& Target[1] | FLT3 0.22 μM (IC50) | c-Kit 0.17 μM (IC50) | PDGFR 0.2 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 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(166.90 mM) H2O : 100 mg/mL(166.90 mM;Need ultrasonic) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 1.6690 mL | 8.3450 mL | 16.6900 mL | 5 mM | 0.3338 mL | 1.6690 mL | 3.3380 mL | 10 mM | 0.1669 mL | 0.8345 mL | 1.6690 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: PBS Solubility: 100 mg/mL (166.90 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (4.17 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.17 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。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.17 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.17 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。 *以上所有助溶剂都可在本网站选购。
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