Benzofuran derivatives as a novel class of inhibitors of mTOR signaling.

Date publication

mars 2014

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DESAUBRY Laurent

Tous les auteurs :
Salome C, Narbonne V, Ribeiro N, Thuaud F, Serova M, de Gramont A, Faivre S, Raymond E, Desaubry L

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/24445311

Résumé

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 IC(5)(0) comprised between 30 and 140 muM. 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.

Référence

Eur J Med Chem. 2014 Mar 3;74:41-9