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Multitarget inhibitors derived from crosstalk mechanism involving VEGFR2

    Chao Ding

    Department of Chemistry, Tsinghua University, Beijing 100084, PR China

    The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China

    Authors contributed equally

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    ,
    Cunlong Zhang

    The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China

    Shenzhen Kivita Innovative Drug Discovery Institute, Shenzhen 518055, China

    Authors contributed equally

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    ,
    Mingli Zhang

    Department of Chemistry, Tsinghua University, Beijing 100084, PR China

    The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China

    ,
    Yu Zong Chen

    Shenzhen Kivita Innovative Drug Discovery Institute, Shenzhen 518055, China

    ,
    Chunyan Tan

    The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China

    ,
    Ying Tan

    The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China

    &
    Yuyang Jiang

    *Author for correspondence:

    E-mail Address: jiangyy@sz.tsinghua.edu.cn

    The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China

    Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, PR China

    Published Online:https://doi.org/10.4155/fmc.14.112

    Seven VEGFR small-molecule inhibitors have been approved by the US FDA as anticancer drugs, which confirms the therapeutic value of angiogenesis inhibitors. However, much more evidence indicates that VEGFR inhibition alone is usually not sufficient to block the tumor progress. The potential of some agents targeting VEGFR owes partially to the simultaneous inhibition of additional targets in other signaling pathways. In this review, the crosstalk between VEGFR2 and the additional targets in other signaling pathways, such as EGFR, MET, FGFR, PDGFR, c-Kit, Raf, PI3K and HDAC, and the synergistic effects derived from multitarget activities against these crosstalks are discussed. We also briefly describe the multitarget inhibitors in clinical trials or reported in the literature and patents under the different multitarget categories involving VEGFR2.

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