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Title

QUINAZOLINE DERIVATIVE COMPOUND (11D) AS A NOVEL ANGIOGENESIS INHIBITOR INHIBITING VEGFR2 AND BLOCKING VEGFR2-MEDIATED AKT/MTOR /P70S6K SIGNALING PATHWAY

Pages

  411-416

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 mM) for 24 hr.Results: The compound 11d exhibited potent inhibitory activity against VEGFR2 with an IC50 of 5.49 mM. 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.

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    APA: Copy

    LI, ZENG, WANG, BIN, TANG, LIANG, CHEN, SHUANGSHENG, & LI, JUN. (2016). QUINAZOLINE DERIVATIVE COMPOUND (11D) AS A NOVEL ANGIOGENESIS INHIBITOR INHIBITING VEGFR2 AND BLOCKING VEGFR2-MEDIATED AKT/MTOR /P70S6K SIGNALING PATHWAY. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 19(4), 411-416. SID. https://sid.ir/paper/696081/en

    Vancouver: Copy

    LI ZENG, WANG BIN, TANG LIANG, CHEN SHUANGSHENG, LI JUN. QUINAZOLINE DERIVATIVE COMPOUND (11D) AS A NOVEL ANGIOGENESIS INHIBITOR INHIBITING VEGFR2 AND BLOCKING VEGFR2-MEDIATED AKT/MTOR /P70S6K SIGNALING PATHWAY. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES[Internet]. 2016;19(4):411-416. Available from: https://sid.ir/paper/696081/en

    IEEE: Copy

    ZENG LI, BIN WANG, LIANG TANG, SHUANGSHENG CHEN, and JUN LI, “QUINAZOLINE DERIVATIVE COMPOUND (11D) AS A NOVEL ANGIOGENESIS INHIBITOR INHIBITING VEGFR2 AND BLOCKING VEGFR2-MEDIATED AKT/MTOR /P70S6K SIGNALING PATHWAY,” IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol. 19, no. 4, pp. 411–416, 2016, [Online]. Available: https://sid.ir/paper/696081/en

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