SGX-523

Kinase assay

Initial rate constants were measured at 21 °C in the presence of 100 mM HEPES (pH 7.5), 0.3 mg/mL poly(Glu-Tyr) peptide substrate, 10 mM MgCl2, 1 mg/mL bovine serum albumin, 5% DMSO, 20 nM MET-KD and various concentrations of ATP and SGX523. Total reaction volumes (20 μL) were quenched with 20 μL Kinase-Glo detection buffer. Luminescence was detected in a plate-reading luminometer and the results were analyzed by nonlinear regression.

Cell lines

MDCK cells

Preparation method

The solubility of this compound in DMSO is > 18 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0.04, 0.12, 0.36 and 3.0 μM; overnight

Applications

In MDCK canine kidney epithelial cells, SGX-523 prevented HGF-induced cell scattering.

Animal models

Nude mice bearing GTL16 gastric cancer cell xenografts

Dosage form

10, 20, 30, 100 mg/kg, b.i.d., or 60 mg/kg, q.d.; p.o.

Applications

At the dose of ﹥ 10 mg /kg twice daily, SGX523 significantly retarded the growth of GTL16 xenografts. In addition, SGX523 substantially inhibited MET kinase activity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Buchanan SG1, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF,Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K,Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90.