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ID: ALA5113445

Journal: Bioorg Med Chem Lett

Title: Identification and in vitro characterization of a new series of potent and highly selective G9a inhibitors as novel anti-fibroadipogenic agents.

Authors: Randazzo P, Sinisi R, Gornati D, Bertuolo S, Bencheva L, De Matteo M, Nibbio M, Monteagudo E, Turcano L, Bianconi V, Peruzzi G, Summa V, Bresciani A, Mozzetta C, Di Fabio R.

Abstract: A new series of in vitro potent and highly selective histone methyl transferase enzyme G9a inhibitors was obtained. In particular, compound 2a, one the most potent G9a inhibitor identified, was endowed with >130-fold selectivity over GLP and excellent ligand efficiency. Therefore, it may represent a valuable tool compound to validate the role of highly selective G9a inhibitors in different pathological conditions. When 2a was characterized in vitro in cellular models of skeletal muscle differentiation, a relevant increase of myofibers' size and reduction of the fibroadipogenic infiltration were observed, further confirming the therapeutic potential of selective G9a inhibitors for the treatment of Duchenne muscle dystrophy.

CiteXplore: 35718104

DOI: 10.1016/j.bmcl.2022.128858