Document Report Card

ID: ALA2086320

Journal: J Med Chem

Title: New synthetic inhibitors of fatty acid synthase with anticancer activity.

Authors: Turrado C, Puig T, García-Cárceles J, Artola M, Benhamú B, Ortega-Gutiérrez S, Relat J, Oliveras G, Blancafort A, Haro D, Marrero PF, Colomer R, López-Rodríguez ML.

Abstract: Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5-30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC(50) < 50 μM have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 μM), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.

CiteXplore: 22559865

DOI: 10.1021/jm2016045