SGX-523

SGX523 is a exquisitely selective and ATP-competitive MET inhibitor. SGX523 potently inhibits MET with an IC₅₀ of 4 nM and is >1,000-fold selective versus other protein kinases. Antitumor activity^[1]. In Vitro: SGX523 shows ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), K_i=2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), K_i=23 nM]^[1].
SGX523 inhibits the growth of gastric and lung cancer cell lines with amplification of the MET gene but has no effect, even at high micromolar concentration, on cell lines with normal MET gene copy number. TheIC₅₀s of 0.02, 0.113, and 0.035 µM for NSCLC H1993, gastric cncer MKN45, and gastric cancer Hs746T cells, respectively^[1].
The IC₅₀ value for the inhibition of MET autophosphorylation is 0.040 μM in GTL16 cells^[1].
SGX523 (0.5, 1.5, 4.6, 13.7, 41, 123, 370, 1100, 3300, 10000 nM; 1 hour) inhibits MET autophosphorylation without affecting total MET or extracellular signal-regulated kinase protein levels in HGF-stimulated A549 cells^[1]. In Vivo: SGX523 exhibits antitumor activity in vivo. SGX523 inhibits MET-dependent tumor growth^[2].