Identification of Small-Molecule Enhancers of Arginine Methylation Catalyzed by Coactivator-Associated Arginine Methyltransferase 1.
Fiche publication
Date publication
novembre 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CAVARELLI Jean
Tous les auteurs :
Castellano S, Spannhoff A, Milite C, Dal Piaz F, Cheng DH, Tosco A, Viviano M, Yamani A, Cianciulli A, Sala M, Cura V, Cavarelli J, Novellino E, Mai A, Bedford MT, Sbardella G
Lien Pubmed
Résumé
Arginine methylation, is a common post-translational modification that is crucial in modulating gene expression at multiple critical. levels. The arginine methyltransferases (PRMTs) are envisaged as promising druggable targets,: but their role in physiological and pathological pathways is far from being clear due to the limited number of modulators reported to date. In this effort; enzyme activators can be invaluable tools, useful as gain-of-function reagents to interrogate the biological roles. in cells and in vivo of PRMTs. Yet the identification such molecule's is rarely pursued. Herein we describe a series of aryl ureido acetamido indole carboxylates (dubbed "uracandolates"), able to increase the Methylation of histone (H3) or nonhistone (polyadenylate-bihding protein 1, PABP1) substrates induced by coactivator-associated arginine methyltransferase 1 (CARM1), bath in in vitro and cellular settings. To the best of our knowledge, this is the first report of compounds acting as CARM1 activators.
Référence
J Med Chem. 2012 Nov 26;55(22):9875-90