Novel inhibitor for fibroblast growth factor receptor tyrosine kinase

  • Bioorg Med Chem Lett. 2007 Sep 1;17(17):4812-8. doi: 10.1016/j.bmcl.2007.06.058.
Naparat Kammasud  1 ,  Chantana Boonyarat ,  Satoshi Tsunoda ,  Hiroaki Sakurai ,  Ikuo Saiki ,  David S Grierson ,  Opa Vajragupta
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
PMID: 17618113 DOI: 10.1016/j.bmcl.2007.06.058
Abstract

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 microM 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.