2. Academic Validation
  3. Synthesis of novel 1,2,4-triazine scaffold as FAK inhibitors with antitumor activity

Synthesis of novel 1,2,4-triazine scaffold as FAK inhibitors with antitumor activity

  • Bioorg Med Chem Lett. 2017 Apr 15;27(8):1727-1730. doi: 10.1016/j.bmcl.2017.02.072.
Pascal Dao 1,  Daniel Lietha 2,  Mélanie Etheve-Quelquejeu 1,  Christiane Garbay 1,  Huixiong Chen 3
Affiliations

Affiliations

  • 1 CNRS UMR8601, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
  • 2 Cell Signalling and Adhesion Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Calle Melchor Fernández Almagro 3, Madrid 28029, Spain.
  • 3 CNRS UMR8601, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France. Electronic address: huixiong.chen@parisdescartes.fr.
PMID: 28284808 DOI: 10.1016/j.bmcl.2017.02.072
Abstract

A series of 1,3,5-triazinic inhibitors of focal adhesion kinase (FAK) has recently been shown to exert antiangiogenic activity against HUVEC cells and Anticancer efficacy against several Cancer cell lines. In this report, we designed and synthesized a series of new compounds containing a 1,2,4-triazine core as novel scaffold for FAK inhibitors. These compounds displayed 10-7M IC50 values, and the best one showed IC50 value of 0.23μM against FAK enzymatic activity. Among them, several inhibitors potently inhibited the proliferation of glioblastoma (U-87MG) and colon (HCT-116) Cancer cell lines. Docking of compound 10 into the active site of the FAK kinase was performed to explore its potential binding mode.

Keywords

1,2,4-Triazines; Anti-cancer activity; FAK inhibitors; Molecular docking; Synthesis.

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