Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/173502
Title: | New synthetic inhibitors of fatty acid synthase with anticancer activity |
Author: | Turrado, Carlos Puig i Miquel, Teresa García-Cárceles, Javier Artola Pino, Marta Benhamú, Bellinda Ortega-Gutiérrez, Silvia Relat Pardo, Joana Oliveras Serrat, Glòria Blancafort, Adriana Haro Bautista, Diego Marrero González, Pedro F. Colomer Bosch, Ramón López-Rodríguez, María Luz |
Keywords: | Àcids grassos Metabolisme Inhibidors enzimàtics Fatty acids Metabolism Enzyme inhibitors |
Issue Date: | 4-May-2012 |
Publisher: | American Chemical Society |
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 IC50 < 50 M have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 M), 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1021/jm2016045 |
It is part of: | Journal of Medicinal Chemistry, 2012, vol. 55, num. 11, p. 5013-5023 |
URI: | http://hdl.handle.net/2445/173502 |
Related resource: | https://doi.org/10.1021/jm2016045 |
ISSN: | 0022-2623 |
Appears in Collections: | Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia) |
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