Rational Adaptation of L3MBTL1 Inhibitors to Create Small-Molecule Cbx7 Antagonists.
ChemMedChem
; 14(15): 1444-1456, 2019 08 06.
Article
em En
| MEDLINE
| ID: mdl-31254321
ABSTRACT
Chromobox homologâ
7 (Cbx7) is an epigenetic modulator that is an important driver of multiple cancers. It is a methyl reader protein that operates by recognizing and binding to methylated lysine residues on specific partners. Herein we report our efforts to create low-molecular-weight inhibitors of Cbx7 by making rational structural adaptations to inhibitors of a different methyl reader protein, L3MBTL1, inhibitors that had previously been reported to be inactive against Cbx7. We evaluated each new inhibitor for Cbx7 inhibition by fluorescence polarization assay, and also confirmed the binding of selected inhibitors to Cbx7 by saturation-transfer difference NMR spectroscopy. This work identified multiple small-molecule inhibitors with modest (IC50 257-500â
µm) potency.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Sulfonamidas
/
Niacinamida
/
Proteínas Supressoras de Tumor
/
Inibidores Enzimáticos
/
Complexo Repressor Polycomb 1
/
Lisina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Ano de publicação:
2019
Tipo de documento:
Article