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Chemical Structure| 1352608-82-2 Chemical Structure| 1352608-82-2

Structure of Vactosertib
CAS No.: 1352608-82-2

Chemical Structure| 1352608-82-2

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EW-7197 is a selective inhibitor of TGF-β receptor ALK4 and ALK5 with IC50s of 13 nM and 11 nM.

Synonyms: EW 7197; TEW-7197; EW-7197

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Product Details of Vactosertib

CAS No. :1352608-82-2
Formula : C22H18FN7
M.W : 399.42
SMILES Code : CC1=CC=CC(C2=C(C3=CN4C(C=C3)=NC=N4)N=C(CNC5=CC=CC=C5F)N2)=N1
Synonyms :
EW 7197; TEW-7197; EW-7197
MDL No. :MFCD28348363
InChI Key :FJCDSQATIJKQKA-UHFFFAOYSA-N
Pubchem ID :54766013

Safety of Vactosertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • TGFβRI/ALK5

    ALK5, IC50:11 nM

  • ALK4

    ALK4, IC50:13 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MDA-MB-231 cells 1 μM 48 hours To evaluate the effect of Vactosertib on cell proliferation, and the results showed significant inhibition of cell proliferation. PMC11337916
A549 cells 0.5 μM 24 hours To investigate the effect of Vactosertib on cell apoptosis, and the results indicated an increased rate of apoptosis. PMC11337916
Human pancreatic cancer cells 1 μM 48 hours To evaluate the inhibitory effect of Vactosertib on pancreatic cancer cell proliferation, results showed significant reduction in cell proliferation PMC10404525
Human breast cancer cells 0.5 μM 24 hours To investigate the effect of Vactosertib on breast cancer cell apoptosis, results showed significant increase in apoptosis PMC10404525
AML12 mouse hepatocytes 0.5 μM 24 hours EW-7197 improved TGF-β-induced cell morphological changes and reduced TGF-β-induced expression of α-SMA, Col I, and p-SMAD2/3. PMC10404525
LX-2 human hepatic stellate cells 0.5 μM 24 hours EW-7197 reduced TGF-β-induced expression of α-SMA, Col I, and p-SMAD2/3, indicating its anti-fibrotic effects. PMC10404525
Panc02 murine pancreatic cancer cells 500 ng/ml 48 hours Combination treatment of Vactosertib and T1-44 significantly inhibited TGF-β-induced cell migration PMC9918730
SNU2491 human pancreatic cancer cells 500 ng/ml 48 hours Combination treatment of Vactosertib and T1-44 significantly inhibited TGF-β-induced cell migration PMC9918730
PDAC cells 80 μM one week To investigate the inhibitory effect of Vactosertib on TGF-β signaling pathway PMC9609288
Mouse osteosarcoma cells 0.79-2.1 μM Inhibition of osteosarcoma cell growth PMC11337916
Human osteosarcoma cells 0.79-2.1 μM Inhibition of osteosarcoma cell growth PMC11337916
SAOS2 cells 0.1 µM Regulation of gene expression, inhibition of osteosarcoma progression and metastasis PMC11337916

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Breast cancer xenograft model Oral 50 mg/kg Once daily for 21 days To assess the effect of Vactosertib on tumor growth, and the results showed a significant reduction in tumor volume. PMC11337916
BALB/c nude mice Pancreatic cancer xenograft model Oral 50 mg/kg Once daily for 21 days To evaluate the anti-tumor effect of Vactosertib in vivo, results showed significant reduction in tumor volume PMC10404525
C57BL/6 mice pancreatic cancer model Oral 25 mg/kg 5 days a week for 4 weeks Combination treatment of Vactosertib and T1-44 significantly reduced tumor growth and invasion, and improved survival in mice PMC9918730
Nude mice SAOS2 osteosarcoma model Oral 50 mg/kg 5 days/week, duration not specified Inhibition of osteosarcoma growth, reduction in tumor volume and metastasis PMC11337916
Nude mice pancreatic cancer metastasis model intraperitoneal injection 40 mg/kg twice a week for three weeks To evaluate the inhibitory effect of Vactosertib on pancreatic cancer metastasis, results showed that Vactosertib completely abrogated lung metastasis primarily originating from LAMC2-expressing cells. PMC9609288
C57BL/6J mice Non-alcoholic steatohepatitis (NASH) model Oral 20 mg/kg Once every 2 days for 6 weeks Co-administration of EW-7197 and Cur5-8 alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score. PMC10404525

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03704675 Healthy Volunteers PHASE1 COMPLETED 2018-10-20 Inje University Busan Paik Hos... More >>pital, Busan, 47392, Korea, Republic of Less <<
NCT03698825 Metastatic Gastric Cancer PHASE1|PHASE2 COMPLETED 2022-12-28 Hallym University Medical Cent... More >>er, Anyang-si, Korea, Republic of|Hwasun Chunnam university hospital, Hwasun, Korea, Republic of|Chung-Ang University hospital, Seoul, Korea, Republic of|Gangbuk Samsung Medical Center, Seoul, Korea, Republic of|Gangnam Severance, Seoul, Korea, Republic of|Shinchon Severance, Seoul, Korea, Republic of Less <<
NCT04258072 Pancreas Cancer PHASE1 UNKNOWN 2025-03-23 Samsung Medical Center, Seoul,... More >> 135-710, Korea, Republic of Less <<
NCT04103645 Myeloproliferative Neoplasm PHASE2 TERMINATED 2024-07-10 Weill Medical College of Corne... More >>ll University, New York, New York, 10021, United States Less <<
NCT02160106 Advanced Stage Solid Tumors PHASE1 COMPLETED 2018-08-28 Durham, North Carolina, 27710,... More >> United States|Nashville, Tennessee, 37203, United States|Nashville, Tennessee, 37232, United States Less <<
NCT04656002 Gastric Cancer PHASE2 UNKNOWN 2025-12-24 -
NCT03074006 Myelodysplastic Syndromes PHASE1 COMPLETED 2019-12-31 Site 03, Tampa, Florida, 33612... More >>, United States|Site 02, Baltimore, Maryland, 21201, United States|Site 01, Bronx, New York, 10461, United States Less <<
NCT03666832 Metastatic Pancreatic Cancer PHASE1|PHASE2 UNKNOWN 2023-12-30 Samsung Medical Center, Seoul,... More >> 135-710, Korea, Republic of Less <<
NCT05588648 Osteosarcoma PHASE1|PHASE2 RECRUITING 2025-11-25 Kaiser Permanente, Roseville, ... More >>California, 95661, United States|Washington University - St. Louis, Saint Louis, Missouri, 63110, United States|UH Rainbow Babies & Children's Hospital, Cleveland, Ohio, 44106, United States|The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States|National Cancer Center, Gyeonggi-do, Korea, Republic of|Korea Institute of Radiological & Medical Sciences, Seoul, Korea, Republic of Less <<
NCT03724851 Metastatic Colorectal Cancer|G... More >>astric Cancer|Gastroesophageal Junction Adenocarcinoma Less << PHASE1|PHASE2 ACTIVE_NOT_RECRUITING 2025-01-31 Asan Medical Center, Seoul, 05... More >>505, Korea, Republic of Less <<
NCT03732274 Non-Small Cell Lung Cancer Met... More >>astatic Less << PHASE1|PHASE2 ACTIVE_NOT_RECRUITING 2024-12-23 ChungBuk national university h... More >>ospital, Chungju, Korea, Republic of|National Cancer Center, Goyang-si, Korea, Republic of|Yeonsei University Hospotal, Seoul, Korea, Republic of|The Catholic univ of korea st.vincent's hospital, Suwon, Korea, Republic of Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.50mL

0.50mL

0.25mL

12.52mL

2.50mL

1.25mL

25.04mL

5.01mL

2.50mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Jin CH, Krishnaiah M, et al. 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.

[2]Son JY, Park SY, 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.

[3]Yoon JH, Jung SM, et al. 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.

[4]Jun EJ, Park JH, et al. EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus. Gastrointest Endosc. 2017 Jul;86(1):219-228.

[5]Naka K, Ishihara 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.

[6]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. PMID: 24786585.

[7]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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