Novel inhibitor for fibroblast growth factor receptor tyrosine kinase

NP603, the 6-dimethoxy phenyl indolin-2-one, was designed as FGF receptor 1 inhibitor by computational study. NP603 was synthesized and found to be more active against endothelial proliferation of HUVEC after the rhFGF-2 stimulation than SU6668 with minimum effective dose of 0.4 μM but with similar potency as SU16g. NP603 inhibited the tyrosine phosphorylation in FGF receptor and the activation of extracellular signal-regulated kinase and c-Jun-N-terminal-kinase after the rhFGF-2 stimulation. The increase in activity of NP603 supports the role of Lys514 movement in ligand–receptor binding in modeling study as the movement accommodates the hydrophobic interaction at the receptor pocket leading to the enhancement of binding capacity.

NP603 was designed as FGF receptor 1 inhibitor by computational study.Figure optionsDownload as PowerPoint slide