BioScience Trends
Online ISSN : 1881-7823
Print ISSN : 1881-7815
ISSN-L : 1881-7815
Original Article
Novel conjugates of endoperoxide and 4-anilinoquinazoline induce myeloma cell apoptosis by inhibiting the IGF1-R/AKT/mTOR signaling pathway
Yujia XuKun ZengXiaoge WangJieyu ZhangBiyin CaoZubin ZhangChunhua QiaoXiaofeng XuQi WangYuanying ZengXinliang Mao
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2020 Volume 14 Issue 2 Pages 96-103

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Abstract

4-anilinoquinazoline-containing inhibitors of the epidermal growth factor receptor (EGFR) are widely used in non-small cell lung cancer patients with mutated EGFR, but they are less effective in multiple myeloma (MM), a fatal malignancy derived from plasma cells. The present study designed a series of novel compounds by conjugating a peroxide bridge to the 4-anilinoquinazoline pharmacophore. Further studies showed that these agents such as 4061 and 4065B displayed potent activity to induce MM cell apoptosis by upregulating pro-apoptotic p53 and Bax while downregulating pro-survival Bcl-2. The mechanistic analysis revealed that both 4061 and 4065B inhibited IGF1-R, AKT and mTOR activation in a concentration dependent manner but had no effects on the expression of their total proteins, suggesting the conjugates of endoperoxide and 4-anilinoquinazoline may exert its anti-myeloma activity by targeting the IGF1-R/AKT/mTOR pathway.

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© 2020 International Research and Cooperation Association for Bio & Socio-Sciences Advancement
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