TEW-7197, a potent ALK5 inhibitor.

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.

Product information

CAS Number: 1352608-82-2

Molecular Weight: 399.42

Formula: C22H18FN7

Synonym:

TEW7197

TEW 7197

TEW-7197

Vactosertib

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

Smiles: CC1=CC=CC(=N1)C1NC(CNC2=CC=CC=C2F)=NC=1C1=CN2N=CN=C2C=C1

InChiKey: FJCDSQATIJKQKA-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: white solid powder

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥24 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. Vactosertib suppresses the TGFβ-induced nuclear translocation of Smad2/3 in 4T1 cells and MCF10A cells. The IC50 value of Vactosertib on pSmad3 in 4T1 cells is 10-30 nM. Vactosertib abrogates TGFb1-induced tumor cell migration and invasion. 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).

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. 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.

References:

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. 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.
3. 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.
4. 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.

Products are for research use only. Not for human use.