Publication: 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases
Issued Date
2009-02-01
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ISSN
0960894X
Other identifier(s)
2-s2.0-58549102475
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Mahidol University
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SCOPUS
Bibliographic Citation
Bioorganic and Medicinal Chemistry Letters. Vol.19, No.3 (2009), 745-750
Suggested Citation
Naparat Kammasud, Chantana Boonyarat, Kingkan Sanphanya, Maleeruk Utsintong, Satoshi Tsunoda, Hiroaki Sakurai, Ikuo Saiki, Isabelle André, David S. Grierson, Opa Vajragupta 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases. Bioorganic and Medicinal Chemistry Letters. Vol.19, No.3 (2009), 745-750. doi:10.1016/j.bmcl.2008.12.023 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27293
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Title
5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases
Abstract
NP506, 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.