SGX523

The hepatocyte growth factor receptor c-Met commonly shows elevated activity in several forms of cancer.^1,2 SGX523 is a potent, selective, ATP-competitive inhibitor that blocks the tyrosine kinase activity of c-Met with an IC₅₀ value of 4 nM.¹ It is over 1,000-fold selective for c-Met over a panel of other kinases.¹ SGX523 is orally active and dose-dependently inhibits the growth of a variety of tumor xenografts in mice.^1,3 The effectiveness of SGX523 is enhanced when combined with other chemotherapeutic compounds, including inhibitors of EGFR.^2,4 SGX523 is metabolized, at least in part, by aldehyde oxidase, an enzyme that differs in activity across different species.⁵

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1. Buchanan, S.G., Hendle, J., Lee, P.S., et al. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol. Cancer Ther. 8(12), 3181-3190 (2009).

2. Padda, S., Neal, J.W., and Wakelee, H.A. MET inhibitors in combination with other therapies in non-small cell lung cancer. Transl. Lung Cancer Res. 1(4), 238-253 (2012).

3. Guessous, F., Zhang, Y., diPierro, C., et al. An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anticancer Agents Med. Chem. 10(1), 28-35 (2010).

4. Zhang, Y.W., Staal, B., Essenburg, C., et al. Strengthening context-dependent anticancer effects on non-small cell lung carcinoma by inhibition of both MET and EGFR. Mol. Cancer Ther. 12(8), 1429-1441 (2013).

5. Diamond, S., Boer, J., Maduskuie, T.P., Jr., et al. Species-specific metabolism of SGX523 by aldehyde oxidase and the toxicological implications. Drug Metab. Dispos. 38(8), 1277-1285 (2010).