Benzofuran derivatives as a novel class of inhibitors of mTOR signaling

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 mu M. 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. (C) 2013 Elsevier Masson SAS. All rights reserved.