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: desaubry@unistra.fr.

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.

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