Benzofuran derivatives as a novel class of inhibitors of mTOR signaling

  • Eur J Med Chem. 2014 Mar 3:74:41-9. doi: 10.1016/j.ejmech.2013.12.020.
Christophe Salomé  1 ,  Vanessa Narbonne  1 ,  Nigel Ribeiro  1 ,  Frédéric Thuaud  1 ,  Maria Serova  2 ,  Armand de Gramont  2 ,  Sandrine Faivre  2 ,  Eric Raymond  2 ,  Laurent Désaubry  3
Affiliations
  • 1. Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France.
  • 2. Department of Medical Oncology, Beaujon University Hospital, INSERM U728/AP-HP, Clichy, France.
  • 3. Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France. Electronic address: [email protected].
PMID: 24445311 DOI: 10.1016/j.ejmech.2013.12.020
Abstract

High-throughput screening (HTS) hit 1 was previously identified as an inhibitor of the Akt/mTOR (Akt/mammalian target of rapamycin) signaling, which is a major target in oncology. The cytotoxicity of 1 was determined on a panel of human Cancer cells lines with an IC₅₀ comprised between 30 and 140 μM. Subsequent structure--activity relationship (SAR) studies led us to the identification of compounds that displayed an enhanced cytotoxicity. We demonstrated also that these molecules directly bind to mTOR complex 1 (mTORC1) and inhibit its kinase activity.

Keywords
Benzofuran; Cytotoxicity; mTOR; mTORC1.