Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics*.
ChemMedChem
; 16(7): 1116-1125, 2021 04 08.
Article
em En
| MEDLINE
| ID: mdl-33513288
ABSTRACT
Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure-activity relationships for this class of compounds.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
/
Desenho de Fármacos
/
Alanina
/
Inibidores Enzimáticos
/
Indóis
/
Neoplasias
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá