2. Academic Validation
  3. Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors

Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors

  • Eur J Med Chem. 2017 Dec 1:141:373-385. doi: 10.1016/j.ejmech.2017.10.008.
Ying Sun 1,  Yuanyuan Shan 2,  Chuansheng Li 1,  Ru Si 1,  Xiaoyan Pan 1,  Binghe Wang 3,  Jie Zhang 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, 710061, China.
  • 2 Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
  • 3 Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, United States.
  • 4 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, 710061, China. Electronic address: zhj8623@xjtu.edu.cn.
PMID: 29032031 DOI: 10.1016/j.ejmech.2017.10.008
Abstract

VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and Anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti-proliferation against a broad spectrum of Cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, TIE-2, and EphB4.

Keywords

1H-indazol-3-amine; Anti-angiogenesis agents; Hinge-binding group; Multi-target; RTK inhibitors.

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