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Publication : Journal of medicinal chemistry

Design, synthesis, and evaluation of novel imidazo[1,2-a][1,3,5]triazines and their derivatives as focal adhesion kinase inhibitors with antitumor activity

Domaines Scientifiques
Maladies
Organismes
Applications
Technique

Publié sur Journal of medicinal chemistry - 11 sept. 2014

Dao P, Smith N, Tomkiewicz-Raulet C, Yen-Pon E, Camacho-Artacho M, Lietha D, Herbeuval JP, Coumoul X, Garbay C, Chen H

Lien vers Pubmed [PMID] – 25180654

J. Med. Chem. 2015 Jan;58(1):237-51

A series of triazinic inhibitors of focal adhesion kinase (FAK) have been recently shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. We report herein that we further explored the heterocyclic core of these inhibitors by a fused imidazole ring with the triazine to provide imidazo[1,2-a][1,3,5]triazines. Importantly, these new compounds displayed 10(-7)-10(-8) M IC50 values, and the best inhibitor showed IC50 value of 50 nM against FAK enzymatic activity. Several inhibitors potently inhibited the proliferation of a panel of cancer cell lines expressing high levels of FAK. Apoptosis analysis in U87-MG and HCT-116 cell lines suggested that these compounds delayed cell cycle progression by arresting cells in the G2/M phase of the cell cycle, retarding cell growth. Further investigation demonstrated that these compounds strongly inhibited cell-matrix adhesion, migration, and invasion of U87-MG cells.

https://www.ncbi.nlm.nih.gov/pubmed/25180654

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