A_83-01_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries

https://www.360docs.net/doc/1f217876.html, Data Sheet

BIOLOGICAL ACTIVITY:

A 83–01 is a selective inhibitor of TGF–β type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7, with IC 50 values of 12, 45 and 7.5 nM, respectively.

IC50 & Target: IC50: 12 nM (ALK5), 45 nM (ALK4), 7.5 nM (ALK7)

In Vitro: A–83–01 (4 μM) treatment increases myotube formation, the expression of MyHC and the expression of Myf5 and MyoD in C2C12 cells [1]. Expression of pSmad3 is increased by the addition of TGF–β1, and the effects of TGF–β1 are inhibited in ovarian cancer cells by A–83–01. TGF–β1 increases cell motility, adhesion and invasion, while A–83–01 decreases these behaviors in HM–1cells [2]. A–83–01 treatment significantly increases these parameters within 24 h that is positively related to pericyte coverage and tumor cell proliferation. Apparent diffusion coefficient (ADC) determined by diffusion–weighed imaging is decreased by A–83–01

treatment, suggesting the decrease of tumor interstitial fluid pressure [3].In Vivo: A–83–01 (50, 150 and 500 μg/mouse, i.p.) significantly improves survival of the mice without body weight or

neurobehavioral appearances [2]. A–83–01 (0.5 mg/kg, i.p.) shows a significantly stronger antitumor effect in mice bearing M109cells [4].

PROTOCOL (Extracted from published papers and Only for reference)

Cell Assay:[2]HM–1 cells are seeded into a 96–well plate and are incubated for 18 hr. A–83–01 (1 μM) or vehicle are then added for 12hr followed by the addition of TGF–β1 (1 ng/mL) or vehicle for 60 hr. The number of viable cells in each well is examined using the WST–1 assay following the manufacturer's instructions.

Animal Administration: A 83–01 is formulated in PBS with 0.5% DMSO.[2]Female B6C3F1 mice used for the in vivo studies are maintained under specific pathogen–free conditions. To evaluate the effect of A–83–01 on the survival of mice bearing peritoneal dissemination, HM–1 cells (1×106) are injected into the abdominal cavity via the left flank of the mouse. Starting the next day,A–83–01 (150 μg/body) or vehicles (PBS with 0.5% DMSO) are injected into the abdominal cavity three times per week. Mice are

euthanized before reaching the moribund state.References:

[1]. Furutani Y, et al. Role of endogenous TGF–β family in myogenic differentiation of C2C12 cells. J Cell Biochem. 2011 Feb;112(2):614–24.

[2]. Yamamura S, et al. The activated transforming growth factor–beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. Int J Cancer. 2012 Jan 1;130(1):20–8.

[3]. Kawano K, Maitani Y. Tumor permeability of nanocarriers observed by dynamic contrast–enhanced magnetic resonance imaging. Yakugaku Zasshi. 2010Dec;130(12):1679–85.

[4]. Taniguchi Y, et al. Enhanced antitumor efficacy of folate–linked liposomal doxorubicin with TGF–β type I receptor inhibitor. Cancer Sci. 2010 Oct;

Product Name:

A 83–01Cat. No.:

HY-10432CAS No.:

909910-43-6Molecular Formula:

C 25H 19N 5S Molecular Weight:

421.52Target:

TGF–β Receptor; ALK Pathway:

TGF–beta/Smad; Protein Tyrosine Kinase/RTK Solubility:

10 mM in DMSO

101(10):2207–13.

Caution: Product has not been fully validated for medical applications. For research use only.

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