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| 25mg |
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Purity: ≥98%
Vactosertib HCl (formerly EW-7197; EW7197) is a highly potent, selective, and orally bioavailable inhibitor of the TGF-β receptor ALK4/ALK5 with anticancer and immunomodulatory effects. Vactosertib inhibited ALK5 with IC50 value of 0.013 μM in a kinase assay and with IC50 values of 0.0165 and 0.0121 μM 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. A phase I clinical study is under way for multiple myeloma and advanced stage solid tumors.
| ln Vitro |
Treatment with vactosertib (10-1000 nM; 30 minutes; 4T1 cells) inhibits the phosphorylation of Smad2 or Smad3 in 4T1 cells produced by TGFβ in a dose-dependent manner[1]. In 4T1 and MCF10A cells, vactosertib inhibits the nuclear translocation of Smad2/3 caused by TGFβ. Vactosertib's IC50 value on pSmad3 in 4T1 cells ranges from 10 to 30 nM[1]. TGFb1-induced tumor cell migration and invasion are inhibited by vactosertib[1]. TGFβ1 increases the mRNA levels of FN1, HMGA2 (high-mobility group AT-hook 2), SNAI1, and SNAI2 (Snail family zinc finger 1 and 2, respectively) and decreases the mRNA level of CDH1. Additionally, vactosertib eliminates the effects of TGFβ1 on genes linked to the epithelial-to-mesenchymal transition (EMT)[1].
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| ln Vivo |
In MMTV/c-Neu female mice, vactosertib (40 mg/kg; intraperitoneal injection; every other day; for 10 weeks) therapy suppresses lung metastases, cell migration, invasion, and Smad/TGFβ signaling[1]. In addition, vasosertib prevents the epithelial-to-mesenchymal transition (EMT) in 4T1 orthotopic-grafted mice and TGFβ-treated breast cancer cells. Moreover, vactosertib prolongs the survival period of 4T1-Luc and 4T1 breast tumor-bearing mice and increases cytotoxic T lymphocyte activity in 4T1 orthotopic-grafted mice[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. Mol Cancer Ther. 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 |
C22H19CLFN7
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|---|---|
| Molecular Weight |
435.884565591812
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| CAS # |
1352610-25-3
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| Related CAS # |
Vactosertib;1352608-82-2
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| SMILES |
FC1=CC=CC=C1NCC2=NC(C3=CN4C(C=C3)=NC=N4)=C(C5=NC(C)=CC=C5)N2.Cl
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| InChi Key |
UDRJLVATGDHMJM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H18FN7.ClH/c1-14-5-4-8-18(27-14)22-21(15-9-10-20-25-13-26-30(20)12-15)28-19(29-22)11-24-17-7-3-2-6-16(17)23/h2-10,12-13,24H,11H2,1H3,(H,28,29)1H
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| Chemical Name |
N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline
hydrochloride
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| Synonyms |
EW-7197 Hydrochloride EW7197 HCl EW7197 Hydrochloride EW 7197 HClEW 7197 Hydrochloride EW-7197 HCl
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
H2O : ~50 mg/mL (~114.71 mM)
DMSO : ~50 mg/mL (~114.71 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 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 (5.74 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 (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 65 mg/mL (149.12 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2942 mL | 11.4710 mL | 22.9421 mL | |
| 5 mM | 0.4588 mL | 2.2942 mL | 4.5884 mL | |
| 10 mM | 0.2294 mL | 1.1471 mL | 2.2942 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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