SGX-523

In vitro potency data against MET are for the kinase domain only and not the full-length enzyme.

SGX523 potently inhibited MET with an IC₅₀ of 4 nM and is >250-fold selective versus 213 other protein kinases, representing approximately half of all catalytically competent human protein kinases and three quarters of all human protein tyrosine kinases. Cellular activity against MET-dependent cell lines was reported as EC₅₀ = 5-113 nM. In vivo target engagement and tumor-growth inhibition were reported following oral administration to mice (10-100 mg/kg dosed twice daily).

From a chemists point of view, this compound is a good probe.

This is an excellent probe molecule. It was highlighted in the famous Nature Biotechnology kinase inhibitor article (Nature Biotechnology 2011, 29, 1046–1051) as one of the most selective kinase inhibitors known. It shows both pharmacodynamic and functional cellular potency in line with its biochemical data as well as robust dose-responsive tumor-growth inhibitory effects in relevant xenograft mouse models. In terms of pre-clinical species, there are no limitations using this compounds in rodents and dog. Selectivity and cellular activity are appropriate for use of this compound as a probe.