quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting vegfr2 and blocking vegfr2-mediated akt/mtor /p70s6k signaling pathway

objective(s): we previously reported a series of quinazoline derivatives as vascular-targeting anticancer agents. in this study, we investigated the mechanism underlying the anti-angiogenic activity of the quinazoline derivative compound 11d. materials and methods: we examined the effects of quinazoline derivative 11d on vascular endothelial growth factor receptor-2 (vegfr2) activation via vegfr2-specific activation assay. reverse transcription and immunohistochemistry were used to detect vascular endothelial growth factor (vegf), vegfr2, and the vegfr2-mediated akt/mtor/p70s6k signaling pathway in human umbilical vascular endothelial cells and hepatocellular carcinoma cells (hepg-2) after treatment with various concentrations of 11d (0, 6.25, 12.5, and 25 μm) for 24 hr. results: the compound 11d exhibited potent inhibitory activity against vegfr2 with an ic50 of 5.49 μm. this compound significantly downregulated vegf, vegfr2, and the vegfr2-mediated akt/mtor/p70s6k signaling pathway in vitro. conclusion:the mechanism underlying the anti-angiogenic activity of the quinazoline derivative 11d possibly involves the inhibition of vegfr2 and the downregulation of vegf, vegfr2, and the vegfr2-mediated akt/mtor/p70s6k signaling pathway. overall, the findings indicate that the studied class of compounds is a source of potential antiproliferative and anti-angiogenic agents, which must be further investigated.