Vactosertib (TEW-7197)

Catalog No.S7530 Batch:S753007

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Technical Data

Formula

C22H18FN7
Molecular Weight 399.42 CAS No. 1352608-82-2
Solubility (25°C)* In vitro DMSO 80 mg/mL (200.29 mM)
Ethanol 27 mg/mL (67.59 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Vactosertib  (TEW-7197, EW-7197) is a highly potent, selective, and orally bioavailable TGF-β receptor ALK4/ALK5 inhibitor with IC50 of 13 nM and 11 nM, respectively. Phase 1.
Targets
ALK5 [1]
(Cell-free assay)		 ALK4 [1]
(Cell-free assay)
11 nM 13 nM
In vitro In HaCaT (3TP-luc) and 4T1 (3TP-luc) stable cells, 12b potently inhibits the TGF-β1-induced luciferase reporter activity with IC50 of 16.5 and 12.1 nM, respectively. [1] EW-7197 inhibits TGFβ-induced Smad2 or Smad3 phosphorylation and the epithelial-to-mesenchymal transition (EMT) in TGFβ-treated breast cancer cells. In addition, EW-7197 also abrogates TGFβ1-induced tumor cell migration and invasion in breast cells. [3]
In vivo In rats, EW-7197 shows an oral bioavailability of 51% with high systemic exposure (AUC) of 1426 ng×h/mL and maximum plasma concentration (Cmax) of 1620 ng/mL. EW-7197 also shows low toxicity on the cardiovascular system, central nervous system, and respiratory system. [1] In a mouse B16 melanoma model, EW-7197 (2.5 mg/kg daily p.o.) suppresses the progression of melanoma with enhanced cytotoxic T-lymphocyte (CTL) responses. [2] EW-7197 enhances cytotoxic T lymphocyte activity in 4T1 orthotopic-grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor-bearing mice. [3]

Protocol (from reference)

Kinase Assay:

[1]
  • Protein Kinase Assay

    A radioisotopic protein kinase assay (HotSpot assay) is performed at Reaction Biology Corporation.

Cell Assay:

[3]
  • Cell lines

    4T1 and MCF10A cells

  • Concentrations

    ~5 μM

  • Incubation Time

    72 hours

  • Method

    Cells are seeded in 96 well plate and treated with indicated concentrations of EW-7197 in 0.2% HI-FBS medium for 72 h. Cells are dried after incubation with 10% TCA in media. Then, cells are incubated with 0.4% SRB (Sulforhodamine B) in 1% acetic acid for 30 min. After washing with 1% glacial acetic acid, bounded dye is released in 10 mM Tris buffer (pH 10.5) for 30 min. Absorbance is measured at 570 nm.
Animal Study:

[2]
  • Animal Models

    Mouse B16 melanoma model

  • Dosages

    2.5 mg/kg daily

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Lab Invest, 2017, 97(3):232-242]

Selleck's Vactosertib (TEW-7197) has been cited by 23 publications

The TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide in relapsed/refractory multiple myeloma: a phase 1b trial [ Nat Commun, 2024, 15(1):7388] PubMed: 39191755
Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma [ Cells, 2024, 13(10)879] PubMed: 38786100
Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma [ Cells, 2024, 13(10)879] PubMed: 38786100
Development of an automated high-content immuno-fluorescence assay of pSmads quantification: proof-of-concept with drugs inhibiting the BMP/TGFbeta pathways [ bioRxiv, 2023, 10.1101/2023.12.14.571626] PubMed: none
Vactosertib, a novel TGF-β1 type I receptor kinase inhibitor, improves T-cell fitness: a single-arm, phase 1b trial in relapsed/refractory multiple myeloma [ Res Sq, 2023, rs.3.rs-3112163] PubMed: 37503043
TGFβR-1/ALK5 inhibitor RepSox induces enteric glia-to-neuron transition and influences gastrointestinal mobility in adult mice [ Acta Pharmacol Sin, 2022, 10.1038/s41401-022-00932-4] PubMed: 35794374
Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression [ Viruses, 2022, 14(6)1308] PubMed: 35746781
Dysregulated myokines and signaling pathways in skeletal muscle dysfunction in a cigarette smoke-induced model of chronic obstructive pulmonary disease [ Front Physiol, 2022, 13:929926] PubMed: 36091368
Myostatin/HIF2α-Mediated Ferroptosis is Involved in Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease [ Int J Chron Obstruct Pulmon Dis, 2022, 17:2383-2399] PubMed: 36185172
Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms [ Cancer Cell, 2021, S1535-6108(21)00492-X] PubMed: 34624218

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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