2. Academic Validation
  3. Discovery of novel anti-angiogenesis agents. Part 10: Multi-target inhibitors of VEGFR-2, Tie-2 and EphB4 incorporated with 1,2,3-triazol

Discovery of novel anti-angiogenesis agents. Part 10: Multi-target inhibitors of VEGFR-2, Tie-2 and EphB4 incorporated with 1,2,3-triazol

  • Eur J Med Chem. 2019 Feb 1:163:1-9. doi: 10.1016/j.ejmech.2018.11.042.
Xiaoyan Pan 1,  Liyuan Liang 1,  Ru Si 1,  Jin Wang 1,  Qingqing Zhang 1,  Huaxin Zhou 1,  Lin Zhang 1,  Jie Zhang 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
  • 2 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: zhj8623@mail.xjtu.edu.cn.
PMID: 30503935 DOI: 10.1016/j.ejmech.2018.11.042
Abstract

VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we developed a series of pyridines incorporated with 1,2,3-triazole as multi-target inhibitors based on the crystal structure alignment of the kinase domain of angiogenic RTKs. Biological results indicated that these multi-target inhibitors displayed considerable potential as novel anti-angiogenic agents. Among them, compound BD7 exhibited the most potent inhibition against the three RTKs simultaneously, and good activity on inhibiting viability of human umbilical endothelial cells. Therefore, 1,2,3-triazole could serve as a promising DFG binding group for multi-target inhibitors of VEGFR-2, TIE-2 and EphB4 bearing pyridine as hinge binding group.

Keywords

1,2,3-Triazole; Anti-angiogenic agents; DFG-binding group; Multi-target; Triple RTK inhibitors.

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