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