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Science China Life Sciences

, Volume 60, Issue 2, pp 202–214 | Cite as

A novel synthetic small molecule YF-452 inhibits tumor growth through antiangiogenesis by suppressing VEGF receptor 2 signaling

  • Yongrui Liu
  • Yuan He
  • Feifei Yang
  • Xiaonan Cong
  • Jinhua Wang
  • Shihong Peng
  • Dan Gao
  • Weifang Wang
  • Liping Lan
  • Xuexiang Ying
  • Mingyao Liu
  • Yihua Chen
  • Zhengfang Yi
Research Paper

Abstract

Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway. In this study, we established a high-profile compounds library and certificated a novel compound named N-(N-pyrrolidylacetyl)-9-(4-bromobenzyl)-1,3,4,9-tetrahydro-β-carboline (YF-452), which remarkably inhibited the migration, invasion and tube-like structure formation of human umbilical vein endothelial cells (HUVECs) with little toxicity invitro. Rat thoracic aorta ring assay indicated that YF-452 significantly blocked the formation of microvascular exvivo. In addition, YF-452 inhibited angiogenesis in chick chorioallantoic membrane (CAM) and mouse corneal micropocket assays. Moreover, YF-452 remarkably suppressed tumor growth in xenografts mice model. Furthermore, investigation of molecular mechanism revealed that YF-452 inhibited VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including extracellular signal regulated kinase (ERK), focal adhesion kinase (FAK) and Src. These results indicate that YF-452 inhibits angiogenesis and may be a potential antiangiogenic drug candidate for cancer therapy.

Keywords

YF-452 angiogenesis HUVECs VEGFR2 

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Notes

Acknowledgements

This work was supported by Major State Basic Research Development Program of China (2015CB910400), National Natural Science Foundation of China (81272463, 81472788, 81330049, 81673304), and The Science and Technology Commission of Shanghai Municipality (15431902200).

Supplementary material

11427_2016_369_MOESM1_ESM.pdf (990 kb)
Migration inhibitory rate of selected 9 compounds

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Copyright information

© Science in China Press and Springer-Verlag GmbH 2017

Authors and Affiliations

  • Yongrui Liu
    • 1
  • Yuan He
    • 1
  • Feifei Yang
    • 1
  • Xiaonan Cong
    • 1
  • Jinhua Wang
    • 1
  • Shihong Peng
    • 1
  • Dan Gao
    • 1
  • Weifang Wang
    • 1
  • Liping Lan
    • 1
  • Xuexiang Ying
    • 2
  • Mingyao Liu
    • 1
    • 3
  • Yihua Chen
    • 1
  • Zhengfang Yi
    • 1
  1. 1.Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiChina
  2. 2.Department of General SurgeryShanghai Jiaotong University Affiliated Sixth People’s HospitalShanghaiChina
  3. 3.Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology and Department of Molecular and Cellular MedicineTexas A&M University Health Science CenterHoustonUSA

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