Vactosertib (TEW-7197)

製品コードS7530 バッチS753007

化学情報

	Synonyms	EW-7197	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₁₈FN₇
	分子量	399.42	CAS No.	1352608-82-2
Solubility (25°C)*	体外	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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ	Protein Kinase Assay
キナーゼアッセイ	A radioisotopic protein kinase assay (HotSpot assay) is performed at Reaction Biology Corporation.
細胞アッセイ	細胞株	4T1 and MCF10A cells
	濃度	~5 μM
	反応時間	72 hours
	実験の流れ	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.
動物実験	動物モデル	Mouse B16 melanoma model
	投薬量	2.5 mg/kg daily
	投与方法	p.o.

参考

カスタマーフィードバック

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Microglial identity and inflammatory responses are controlled by the combined effects of neurons and astrocytes [ Cell Rep, 2021, 34(12):108882]	PubMed: 33761343
Facile discovery of a therapeutic agent for NK-mediated synergistic antitumor effects using a patient-derived 3D platform [ Biomater Sci, 2021, 10.1039/d1bm01699g]	PubMed: 34940764
Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes [ Front Neurosci, 2021, 15:768262]	PubMed: 34795557

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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