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oai:recercat.cat:2445/1735022025-12-05T14:54:21Zcom_2072_1057col_2072_478917col_2072_478924

New synthetic inhibitors of fatty acid synthase with anticancer activity 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 Àcids grassos Metabolisme Inhibidors enzimàtics Fatty acids Metabolism Enzyme inhibitors 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. 2021-01-28T14:10:48Z 2021-01-28T14:10:48Z 2012-05-04 2021-01-28T14:10:49Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 0022-2623 https://hdl.handle.net/2445/173502 613827 eng Versió postprint del document publicat a: https://doi.org/10.1021/jm2016045 Journal of Medicinal Chemistry, 2012, vol. 55, num. 11, p. 5013-5023 https://doi.org/10.1021/jm2016045 (c) American Chemical Society , 2012 info:eu-repo/semantics/openAccess 11 p. application/pdf American Chemical Society Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)