R428_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries

https://www.wendangku.net/doc/20685246.html, Data Sheet

BIOLOGICAL ACTIVITY:

R428 is a potent and selective inhibitor of Axl with IC 50 value of 14 nM.

IC50 & Target: IC50: 14 nM (Axl kinase)

In Vitro: R428 (2μM) significantly interferes with mechanisms of migration and invasion of Axlpos melanoma cells at levels

comparable to Axl knockdown [1]. R428 synergizes with cisplatin to enhance suppression of liver micrometastasis [2]. R428 (50nM–1μM) causes a concentration–dependent inhibition of preadipocyte differentiation into mature adipocytes, as evidenced by reduced lipid uptake [3].

In Vivo: R428 (125 mg/kg, p.o.) significantly blocks MDA–MB–231–luc–D3H2LN metastases development in two independent mouse models of breast cancer dissemination, suppresses both tumor angiogenesis and vascular endothelial growth factor (VEGF)–induced corneal neovascularization in vivo [2]. R428 (75 mg/kg/day, 25 mg/kg twice daily, p.o.) makes mice keep on a

high–fat diet resulted in significantly reduced weight gain and subcutaneous and gonadal fat mass [3]. PROTOCOL (Extracted from published papers and Only for reference)

Cell Assay: R428 is dissolved in 0.25% DMSO at a concentration of 2 μM.[1]Cells maintained for 24 hours in serum–free medium are harvested and transferred to the upper chamber (1.5×105 cells per well) of uncoated (migration) or matrigel–coated (invasion) 24–well chambers. RPMI medium containing 10% fetal bovine serum is added to the lower chamber. R428 (2 μM) or vehicle (DMSO, 0.25%) is added for 2 hours to cells before loading them in the upper chambers. Both the upper and lower chambers contain the drug or

vehicle. Quantification of migrating/invading cells is obtained by measuring their fluorescent signals with a 480/520 nm filter set on an Infinite M1000 microplate reader 20 or 42 hours later, respectively.

Animal Administration: R428 is formulated in 0.5% hydroxypropylmethylcellulose + 0.1% Tween 80 at a concentration of 125

mg/kg.[2]Seven– to 8–wk–old female NCr nu/nu mice are injected intracardially with bioluminescent MDA–MB–231–luc–D3H2LN cell suspension. Oral dosing with R428 (125 mg/kg, p.o.) or vehicle twice daily begins 2 h before cell implantation and continue to day 21(n=20). Metastatic burden is quantified by in vivo bioluminescence imaging on day 22 and analyzed using the Wilcoxon rank sum test.References:

[1]. Sensi M, et al. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase. J Invest Dermatol. 2011 Dec;131(12):2448–57.

[2]. Holland SJ, et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 2010 Feb 15;70(4):1544–54.

[3]. Lijnen HR, et al. Growth arrest–specific protein 6 receptor antagonism impairs adipocyte differentiation and adipose tissue development in mice. J Pharmacol Exp Ther. 2011 May;337(2):457–64.

Product Name:

R428Cat. No.:

HY-15150CAS No.:

1037624-75-1Molecular Formula:

C 30H 34N 8Molecular Weight:

506.64Target:

TAM Receptor Pathway:

Protein Tyrosine Kinase/RTK Solubility:

DMSO: 10.25 mg/mL

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

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