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

Autor:	Pietro Randazzo, Roberta Sinisi, Davide Gornati, Stefania Bertuolo, Leda Bencheva, Marilenia De Matteo, Martina Nibbio, Edith Monteagudo, Lorenzo Turcano, Valeria Bianconi, Giovanna Peruzzi, Vincenzo Summa, Alberto Bresciani, Chiara Mozzetta, Romano Di Fabio
Přispěvatelé:	Randazzo, Pietro, Sinisi, Roberta, Gornati, Davide, Bertuolo, Stefania, Bencheva, Leda, De Matteo, Marilenia, Nibbio, Martina, Monteagudo, Edith, Turcano, Lorenzo, Bianconi, Valeria, Peruzzi, Giovanna, Summa, Vincenzo, Bresciani, Alberto, Mozzetta, Chiara, Di Fabio, Romano
Rok vydání:	2022
Předmět:	Histones Organic Chemistry Clinical Biochemistry Drug Discovery H3K9 methylation G9a GLP Skeletal muscle regeneration Duchenne muscle dystrophy Pharmaceutical Science Molecular Medicine Histone-Lysine N-Methyltransferase Enzyme Inhibitors Molecular Biology Biochemistry
Zdroj:	Bioorganicmedicinal chemistry letters. 72
ISSN:	1464-3405
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c16f1d726f60b59e9a6c51d4c6d75e5 https://pubmed.ncbi.nlm.nih.gov/35718104 Zobrazit plný text záznamu Full Text from ScienceDirect