NDLI: Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway.

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Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway.

Content Provider	Europe PMC
Author	Li, Zeng Wang, Bin Tang, Liang Chen, Shuangsheng Li, Jun
Copyright Year	2016
Abstract	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.
ISSN	20083866
Journal	Iranian Journal of Basic Medical Sciences
Volume Number	19
PubMed Central reference number	PMC4887714
Issue Number	4
PubMed reference number	27279985
e-ISSN	20083874
Language	English
Publisher	Mashhad University of Medical Sciences
Publisher Date	2016-04-01
Publisher Place	Iran
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright: © Iranian Journal of Basic Medical Sciences
Subject Keyword	anti-angiogenic Akt/mTOR/p70s6k mechanism Quinazoline derivatives VEGF VEGFR2
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Drug Discovery Clinical Biochemistry Biochemistry Biophysics

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Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway

Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway

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