Vactosertib (EW-7197) 是一种有效的，具有口服活性且具有 ATP 竞争性激活素受体样激酶 5 (ALK5) 抑制剂，IC50为 12.9 nM。Vactosertib 还以纳摩尔浓度抑制 ALK2 和 ALK4 (IC50为 17.3 nM)。Vactosertib 具有强大的抗转移活性和抗癌作用。
| 生物活性 | Vactosertib (EW-7197) is a potent, orally active and ATP-competitiveactivin receptor-like kinase 5 (ALK5)inhibitor with anIC50of 12.9 nM. Vactosertib also inhibitsALK2andALK4(IC50of 17.3 nM) at nanomolar concentrations. Vactosertib has potently antimetastatic activity and anticancer effect[1][2]. |
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体外研究
(In Vitro) | Vactosertib (10-1000 nM; 30 minutes; 4T1 cells) treatment blocks the TGFβ-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner in 4T1 cells[1].
Vactosertib suppresses the TGFβ-induced nuclear translocation of Smad2/3 in 4T1 cells and MCF10A cells. TheIC50value of Vactosertib on pSmad3 in 4T1 cells is 10-30 nM[1].
Vactosertib abrogates TGFb1-induced tumor cell migration and invasion[1].
TGFβ1 downregulated the mRNA level of CDH1 and upregulated the mRNA levels of FN1, HMGA2 (high-mobility group AT-hook 2), SNAI1, and SNAI2 (Snail family zinc finger 1 and 2, respectively). Moreover, Vactosertib abolishes the TGFβ1-induced effects on genes related to epithelial-to-mesenchymal transition (EMT)[1].
Western Blot Analysis[1] | Cell Line: | 4T1 cells | | Concentration: | 10 nM, 30 μM, 50 nM, 100 μM, 300 nM, 500 nM, 1000 nM | | Incubation Time: | 30 minutes | | Result: | Blocked the TGFb-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner. |
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体内研究
(In Vivo) | Vactosertib (40 mg/kg; intraperitoneal injection; every other day; for 10 weeks; MMTV/c-Neu female mice) treatment inhibits Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice[1].
Vactosertib also inhibits the epithelial-to-mesenchymal transition (EMT) in both TGFβ-treated breast cancer cells and 4T1 orthotopic-grafted mice. Furthermore, Vactosertib enhances cytotoxic T lymphocyte activity in 4T1 orthotopic-grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor-bearing mice[1].
| Animal Model: | Mammary tumor virus (MMTV)/c-Neu female mice (32-week-old)[1] | | Dosage: | 40 mg/kg | | Administration: | Intraperitoneal injection; every other day; for 10 weeks | | Result: | Inhibited Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice. |
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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 : 100 mg/mL(250.36 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.5036 mL | 12.5182 mL | 25.0363 mL | | 5 mM | 0.5007 mL | 2.5036 mL | 5.0073 mL | | 10 mM | 0.2504 mL | 1.2518 mL | 2.5036 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。-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： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (6.26 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (6.26 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 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 (6.26 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.26 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 (6.26 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.26 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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