Vactosertib
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MedKoo CAT#: 558278

CAS#: 1352608-82-2 (free base)

Description: Vactosertib, also known as TEW-7197 is a potent ALK5 inhibitor. TEW-7197 showed potent in vivo anti-metastatic activity, indicating its potential for use as an anti-cancer therapy. EW-7197 inhibits TGF-β/Smad signaling. EW-7197 abrogates TGF-β1-induced tumor cell migration and invasion. EW-7197 inhibits breast cancer metastasis to the lung.EW-7197 prolongs the life span of BALB/c 4T1 mice via inhibition of EMT. EW-7197 inhibits metastasis and enhances the activity of cytotoxic T lymphocytes (CTLs) in 4T1 orthotopic grafted mice.


Chemical Structure

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Vactosertib
CAS# 1352608-82-2 (free base)

Theoretical Analysis

MedKoo Cat#: 558278
Name: Vactosertib
CAS#: 1352608-82-2 (free base)
Chemical Formula: C22H18FN7
Exact Mass: 399.16077
Molecular Weight: 399.42
Elemental Analysis: C, 66.15; H, 4.54; F, 4.76; N, 24.55

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 850.0 Ready to ship
500.0mg USD 1850.0 Ready to ship
1.0g USD 3250.0 Ready to ship
2.0g USD 5850.0 Ready to ship
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Related CAS #: 1352610-25-3 (HCl)   1352608-82-2 (free base)  

Synonym: TEW7197; TEW 7197; TEW-7197; Vactosertib

IUPAC/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

InChi Key: FJCDSQATIJKQKA-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H18FN7/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)

SMILES Code: FC1=CC=CC=C1NCC2=NC(C3=CN4C(C=C3)=NC=N4)=C(C5=NC(C)=CC=C5)N2

Appearance: white solid powder

Purity: >99% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Vactosertib (EW-7197) is an ATP-competitive activin receptor-like kinase 5 (ALK5) inhibitor with an IC50 of 12.9 nM and also inhibits ALK2 and ALK4 (IC50 of 17.3 nM) at nanomolar concentrations.
In vitro activity: These data indicated that EW-7197 inhibited the growth of HCC cells (Figs. 1A,C) without cytotoxicity. This study compared the activity of EW-7197 with those of other ALK5 inhibitors in SK-HEP1-Lux cells using a reporter gene assay. The assessment of TGF-β1-induced luciferase activity indicated that EW-7197 exerted a more potent inhibitory effect than the other ALK5 inhibitors (Supplementary Fig. S2A). Immunofluorescence and Western blot analysis showed that EW-7197 inhibited the TGF-β1-induced phosphorylation of Smad3 in SK-HEP1, SNU354, HepG2, and Huh7 cells in vitro (Supplementary Figs. S2B and S2C). Reference: Sci Rep. 2015; 5: 16492. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637930/
In vivo activity: Repeated intratunical injections of fibrin induced fibrotic scarring in the TA. PD rats treated with Vactosertib showed a remarkable regression of fibrotic plaques and improved the disorganization of collagen distribution (Fig. 2). H&E and immunohistochemical staining for vimentin revealed infiltration of lymphocytes and fibroblasts in fibrotic plaques of the vehicle-treated PD rats. Oral administration of Vactosertib significantly decreased inflammatory cell infiltration (Fig. 3A). Reference: World J Mens Health. 2020 Oct; 38(4): 552–563. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502315/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 80.0 200.0
Water 0.1 0.25

Preparing Stock Solutions

The following data is based on the product molecular weight 399.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Kim MJ, Park SA, Kim CH, Park SY, Kim JS, Kim DK, Nam JS, Sheen YY. TGF-β Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1α-Induced Epithelial Mesenchymal Transition. Cell Physiol Biochem. 2016;38(2):571-88. doi: 10.1159/000438651. Epub 2016 Feb 5. PMID: 26845171. 2. Park SA, Kim MJ, Park SY, Kim JS, Lim W, Nam JS, Yhong Sheen Y. TIMP-1 mediates TGF-β-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling. Sci Rep. 2015 Nov 9;5:16492. doi: 10.1038/srep16492. PMID: 26549110; PMCID: PMC4637930. 3. Song KM, Chung DY, Choi MJ, Ghatak K, Minh NN, Limanjaya A, Kwon MH, Ock J, Yin GN, Kim DK, Ryu JK, Suh JK. Vactosertib, a Novel, Orally Bioavailable Activin Receptor-Like Kinase 5 Inhibitor, Promotes Regression of Fibrotic Plaques in a Rat Model of Peyronie's Disease. World J Mens Health. 2020 Oct;38(4):552-563. doi: 10.5534/wjmh.190071. Epub 2019 Aug 27. PMID: 31496148; PMCID: PMC7502315. 4. Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, Kim SW, Kim DK, Nam JS, Sheen YY. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16. doi: 10.1158/1535-7163.MCT-13-0903. Epub 2014 May 9. PMID: 24817629.
In vitro protocol: 1. Kim MJ, Park SA, Kim CH, Park SY, Kim JS, Kim DK, Nam JS, Sheen YY. TGF-β Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1α-Induced Epithelial Mesenchymal Transition. Cell Physiol Biochem. 2016;38(2):571-88. doi: 10.1159/000438651. Epub 2016 Feb 5. PMID: 26845171. 2. Park SA, Kim MJ, Park SY, Kim JS, Lim W, Nam JS, Yhong Sheen Y. TIMP-1 mediates TGF-β-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling. Sci Rep. 2015 Nov 9;5:16492. doi: 10.1038/srep16492. PMID: 26549110; PMCID: PMC4637930.
In vivo protocol: 1. Song KM, Chung DY, Choi MJ, Ghatak K, Minh NN, Limanjaya A, Kwon MH, Ock J, Yin GN, Kim DK, Ryu JK, Suh JK. Vactosertib, a Novel, Orally Bioavailable Activin Receptor-Like Kinase 5 Inhibitor, Promotes Regression of Fibrotic Plaques in a Rat Model of Peyronie's Disease. World J Mens Health. 2020 Oct;38(4):552-563. doi: 10.5534/wjmh.190071. Epub 2019 Aug 27. PMID: 31496148; PMCID: PMC7502315. 2. Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, Kim SW, Kim DK, Nam JS, Sheen YY. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16. doi: 10.1158/1535-7163.MCT-13-0903. Epub 2014 May 9. PMID: 24817629.

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1: Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, Kim SW, Kim DK, Nam JS, Sheen YY. EW-7197, A Novel ALK-5 Kinase Inhibitor, Potently Inhibits Breast to Lung Metastasis. Mol Cancer Ther. 2014 May 9. [Epub ahead of print] PubMed PMID: 24817629.

2: Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, Park SJ, Park HJ, Lee K, Sheen YY, Kim DK. Discovery of N-((4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2 -yl)methyl)-2-fluoroaniline (EW-7197): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of TGF-β Type I Receptor Kinase as Cancer Immunotherapeutic/Antifibrotic Agent. J Med Chem. 2014 May 22;57(10):4213-38. doi: 10.1021/jm500115w. Epub 2014 May 13. PubMed PMID: 24786585.

3: Sheen YY, Kim MJ, Park SA, Park SY, Nam JS. Targeting the Transforming Growth Factor-β Signaling in Cancer Therapy. Biomol Ther (Seoul). 2013 Sep 30;21(5):323-331. Review. PubMed PMID: 24244818; PubMed Central PMCID: PMC3825194.

4: Yoon JH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, Sudo K, Nakae S, Han JS, Kim OH, Oh BC, Sumida T, Kuroda M, Ju JH, Jung KC, Park SH, Kim DK, Mamura M. Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med. 2013 Nov;5(11):1720-39. doi: 10.1002/emmm.201302524. Epub 2013 Oct 11. Erratum in: EMBO Mol Med. 2014 May;6(5):703. PubMed PMID: 24127404; PubMed Central PMCID: PMC3840488.



Additional Information