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Purity: ≥98%
Vactosertib (formerly EW-7197; TEW-7197) is a highly potent, selective, ATP-competitive and orally bioavailable inhibitor of the TGF-β receptor ALK4/ALK5 (activin receptor-like kinase) with potential anticancer activity. Vactosertib inhibited ALK5 with an IC50 of 13 nM in a kinase assay and with IC50 values of 165 and 121 nM in HaCaT (3TP-luc) stable cells and 4T1 (3TP-luc) stable cells, respectively, in a luciferase assay. Selectivity profiling of Vactosertib using a panel of 320 protein kinases revealed that it is a highly selective ALK5/ALK4 inhibitor with IC50 values of 13 nM and 11 nM respectively. Pharmacokinetic study with vactosertib in rats showed an oral bioavailability of 51%. Vactosertib has potential anti-cancer activity and is currently undergoing a phase I clinical study for multiple myeloma and advanced stage solid tumors.
| ln Vitro |
Vactosertib (10-1000 nM; 30 minutes; 4T1 cells) treatment suppresses TGFβ-induced Smad2 or Smad3 phosphorylation in 4T1 cells in a dose-dependent manner [1]. In 4T1 and MCF10A cells, vactosertib prevents TGFβ-induced Smad2/3 nuclear translocation. In 4T1 cells, Vactosertib's IC50 value against pSmad3 is 10–30 nM[1]. TGFb1-induced tumor cell migration and invasion can be stopped by vactosertib [1]. TGFβ1 upregulates FN1, HMGA2 (high mobility group AT-hook 2), SNAI1 and SNAI2 (Snail family zinc fingers 1 and 2, respectively) and downregulates CDH1 mRNA levels. Furthermore, TGFβ1-induced effects on genes associated to the epithelial-mesenchymal transition (EMT) were eliminated by vactosertib [1].
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| ln Vivo |
MMTV/c-Neu female mice treated with vabotosertib (40 mg/kg; i.p.; every other day; for 10 weeks) are less likely to exhibit lung metastases, cell migration, invasion, and Smad/TGFβ signaling [1]. Additionally, in 4T1 orthotopically transplanted mice and in breast cancer cells treated with TGFβ, vactosertib suppresses the epithelial-to-mesenchymal transition (EMT). Furthermore, in 4T1 orthotopic transplanted mice, vactosertib can increase the activity of cytotoxic T cells and extend the survival period of 4T1-Luc and 4T1 breast cancer tumor-bearing animals [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: 4T1 cells Tested Concentrations: 10 nM, 30 µM, 50 nM, 100 µM, 300 nM, 500 nM, 1000 nM Incubation Duration: 30 minutes Experimental Results: Blocked the TGFb-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Mammary tumor virus (MMTV)/c-Neu female mice (32weeks old)[1]
Doses: 40 mg/kg Route of Administration: intraperitoneal (ip)injection; every other day; for 10 weeks Experimental Results: Inhibited Smad/TGFβ signaling , cell migration, invasion, and lung metastasis in MMTV/c-Neu mice. |
| References |
[1]. Son JY et al. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis, 2014 Jul, 13(7):1704-16.
[2]. Naka K, et al. Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells. Cancer Sci. 2016 Feb;107(2):140-8. |
| Molecular Formula |
C22H18FN7
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| Molecular Weight |
399.42
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| CAS # |
1352608-82-2
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| Related CAS # |
Vactosertib Hydrochloride;1352610-25-3
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| SMILES |
FC1=CC=CC=C1NCC2=NC(C3=CN4C(C=C3)=NC=N4)=C(C5=NC(C)=CC=C5)N2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.26 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
EW-7197 inhibits TGFβ1/Smad signaling.Mol Cancer Ther.2014 Jul;13(7):1704-16. |
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Effect of EW-7197 on cell migration and invasion.Mol Cancer Ther.2014 Jul;13(7):1704-16. |
Effect of EW-7197 on EMT.Mol Cancer Ther.2014 Jul;13(7):1704-16. |
EW-7197 inhibits breast cancer metastasis to the lung.Mol Cancer Ther.2014 Jul;13(7):1704-16. |
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EW-7197 prolongs the life span of BALB/c 4T1 mice via inhibition of EMT.Mol Cancer Ther.2014 Jul;13(7):1704-16. |
EW-7197 inhibits metastasis and enhances the activity of CTLs in 4T1 orthotopic–grafted mice.Mol Cancer Ther.2014 Jul;13(7):1704-16. |
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