Naparat KammasudChantana BoonyaratKingkan SanphanyaMaleeruk UtsintongSatoshi TsunodaHiroaki SakuraiIkuo SaikiIsabelle AndréDavid S. GriersonOpa VajraguptaMahidol UniversityKhon Kaen UniversityInstitute of Natural MedicineCNRS Centre National de la Recherche Scientifique2018-09-132018-09-132009-02-01Bioorganic and Medicinal Chemistry Letters. Vol.19, No.3 (2009), 745-7500960894X2-s2.0-58549102475https://repository.li.mahidol.ac.th/handle/20.500.14594/27293NP506, the 3-{2,4-dimethyl-5-[2-oxo-5-(N′-phenylhydrazinocarbonyl)-1,2-dihydro-indol-3-ylidenemethyl]-1H-pyrrol-3-yl}-propionic acid, was designed as FGF receptor 1 inhibitor by computational study and found to be more active against endothelial proliferation of HUVEC after the rhFGF-2 stimulation than SU6668 with minimum effective dose of 10 μM. NP506 inhibited the tyrosine phosphorylation in FGF, VEGF, and PDGF receptors and the activation of extracellular signal-regulated kinase (ERK), c-Jun-N-terminal-kinase (JNK) and AKT after the rhFGF-2 stimulation. The introduction of the phenyl hydrazide motif to the position 5 of the pyrido[2,3-d]pyrimidine scaffold led to the inhibitory effect in two signaling pathways: inhibition of AKT activation in the phosphatidyl inositol 3′-kinase (PI13K)/AKT signaling pathway and the inhibition of ERK and JNK activation in MAPK pathway. © 2008 Elsevier Ltd. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.bmcl.2008.12.023