2. Academic Validation
  3. Benzofuran derivatives as anticancer inhibitors of mTOR signaling

Benzofuran derivatives as anticancer inhibitors of mTOR signaling

  • Eur J Med Chem. 2014 Jun 23:81:181-91. doi: 10.1016/j.ejmech.2014.05.014.
Christophe Salomé 1,  Nigel Ribeiro 1,  Thierry Chavagnan 1,  Frédéric Thuaud 1,  Maria Serova 2,  Armand de Gramont 2,  Sandrine Faivre 3,  Eric Raymond 3,  Laurent Désaubry 4
Affiliations

Affiliations

  • 1 Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France.
  • 2 AAREC Filia Research, 1 Place Paul Verlaine, 92100 Boulogne-Billancourt, France.
  • 3 Departments of Medical Oncology, Beaujon University Hospital, INSERM U728/AP-HP, Clichy, France.
  • 4 Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France. Electronic address: desaubry@unistra.fr.
PMID: 24836070 DOI: 10.1016/j.ejmech.2014.05.014
Abstract

A series of 32 derivatives and isosteres of the mTOR Inhibitor 2 were synthesized and compared for their cytotoxicity in radioresistant SQ20B Cancer cell line. Several of these compounds, in particular 30b, were significantly more cytotoxic than 2. Importantly, 30b was shown to block both mTORC1 and Akt signaling, suggesting insensitivity to the resistance associated to Akt overactivation observed with rapamycin derivatives currently used in clinic.

Keywords

Benzofuran; Cancer; Cytotoxicity; Rapamycin; mTOR.

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