Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer.
Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer.
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DOI：
10.1016/j.bmc.2021.116061
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发表时间：
2021-04-01
影响因子：
3.5
通讯作者：
Gangjee A
中科院分区：
文献类型：
--
作者：
Choudhary S;Doshi A;Luckett-Chastain L;Ihnat M;Hamel E;Mooberry SL;Gangjee A
基于喹唑啉的抗胶质瘤药物的疗效归因于它们对微管动力学的影响。描述了喹唑啉类药物作为多种细胞内靶点（包括微管和多种rtk）的有效抑制剂的设计、合成和生物学评价。除了已知的喹唑啉1和2引起微管解聚的能力外，它们还被发现是EGFR、VEGFR-2和PDGFR-β的低纳摩尔抑制剂。1-3和9-10观察到低纳摩尔抑制EGFR。化合物1和4抑制VEGFR-2激酶的活性优于或等于舒尼替尼。此外，化合物1和2在CAM血管生成实验中具有与舒尼替尼相似的效力。本研究中化合物的多靶点活性表明，喹唑啉类药物可以影响多种途径，并可能导致这些药物具有多靶点活性而具有抗肿瘤潜力。
The efficacy of quinazoline-based antiglioma agents has been attributed to their effects on microtubule dynamics. The design, synthesis and biological evaluation of quinazolines as potent inhibitors of multiple intracellular targets, including microtubules and multiple RTKs, is described. In addition to the known ability of quinazolines 1 and 2 to cause microtubule depolymerization, they were found to be low nanomolar inhibitors of EGFR, VEGFR-2 and PDGFR-β. Low nanomolar inhibition of EGFR was observed for 1-3 and 9-10. Compounds 1 and 4 inhibited VEGFR-2 kinase with activity better than or equal to that of sunitinib. In addition, compounds 1 and 2 had similar potency to sunitinib in the CAM angiogenesis assay. Multitarget activities of compounds in the present study demonstrates that the quinazolines can affect multiple pathways and could lead to these agents having antitumor potential caused by their activity against multiple targets.
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影响因子：
2.7
作者：
Devambatla RKV;Li W;Zaware N;Choudhary S;Hamel E;Mooberry SL;Gangjee A
通讯作者：
Gangjee A
影响因子：
5.7
作者：
Bello, Ezia;Taraboletti, Giulia;Damia, Giovanna
通讯作者：
Damia, Giovanna
影响因子：
6.2
作者：
Buchbinder, Elizabeth I.;Sosman, Jeffrey A.;Hodi, F. Stephen
通讯作者：
Hodi, F. Stephen
影响因子：
7.3
作者：
Ganglee, Aleem;Zhao, Ying;Mooberry, Susan L.
通讯作者：
Mooberry, Susan L.
影响因子：
2.9
作者：
HAMEL, E;LIN, CM
通讯作者：
LIN, CM