Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors.
Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors.
复制标题
新型抗血管生成剂的发现。
DOI：
10.1016/j.ejmech.2016.12.059
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发表时间：
2017-02
影响因子：
6.7
通讯作者：
Zhang Jie
中科院分区：
文献类型：
--
作者：
Zhang Lin;Shan Yuanyuan;Li Chuansheng;Sun Ying;Su Ping;Wang Jinfeng;Li Lisha;Pan Xiaoyan;Zhang Jie
血管生成受多种促血管生成因子调节，包括VEGFR-2、Tie-2和EphB 4。而且，他们的相声也是精心制作的。我们已经确定了几种基于二芳基脲的VEGFR-2抑制剂作为潜在的抗血管生成剂。作为我们先前研究的延续，已经开发了两个系列的二芳基丙二酰胺和二芳基硫脲衍生物作为多重VEGFR-2/Tie-2/EphB 4抑制剂。有趣的是，生物学评价表明，几种带有三氟甲基或三氟甲氧基的化合物对血管生成相关的VEGFR-2、Tie-2和EphB 4表现出有希望的多重抑制。代表性化合物（18 a）显示出有效的多靶向RTK抑制和对人脐静脉内皮细胞（EA.hy926）的相当大的抗增殖活性。这些结果将有助于发现新的多靶点抗血管生成药物。
Angiogenesis is modulated by a multitude of pro-angiogenic factors including VEGFR-2, Tie-2, and EphB4. Moreover, their crosstalk also had been well elaborated. We have identified several diarylurea-based VEGFR-2 inhibitors as potential anti-angiogenesis agents. As a continuation to our previous research, two series of diaryl malonamide and diaryl thiourea derivatives have been developed as multiplex VEGFR-2/Tie-2/EphB4 inhibitors. Interestingly, the biological evaluation indicated that several compounds bearing trifluoromethyl or trifluoromethoxyl exhibited promising multiplex inhibition against angiogenesis-related VEGFR-2, Tie-2, and EphB4. The representative compound (18a) displayed both potent multi-targeted RTK inhibition and considerable antiproliferative activities against human umbilical vein endothelial cells (EA.hy926). These results will contribute to the discovery of novel muti-targeted anti-angiogenesis agents.
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影响因子：
2.7
作者：
Jie Zhang;Yanmin Zhang;San-qi Zhang;Sicen Wang;Langchong He
通讯作者：
Jie Zhang;Yanmin Zhang;San-qi Zhang;Sicen Wang;Langchong He
影响因子：
7.3
作者：
Hudkins, Robert L.;Becknell, Nadine C.;Ruggeri, Bruce A.
通讯作者：
Ruggeri, Bruce A.
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.3
作者：
Oike, Y;Ito, Y;Suda, T
通讯作者：
Suda, T
影响因子：
3.4
作者：
Kruger, Albert W.;Rozema, Michael J.;Wang, Zhe
通讯作者：
Wang, Zhe