Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and a Report on a Unique DFG-in/Leu-in Conformation of Mitogen-Activated Protein Kinase Kinase 7 (MKK7).
J Med Chem
; 62(11): 5541-5546, 2019 06 13.
Article
em En
| MEDLINE
| ID: mdl-31083997
ABSTRACT
Pyrazolopyrimidines are well-established as covalent inhibitors of protein kinases such as the epidermal growth factor receptor or Bruton's tyrosine kinase, and we recently described their potential in targeting mitogen-activated protein kinase kinase 7 (MKK7). Herein, we report the structure-activity relationship of pyrazolopyrimidine-based MKK7 inhibitors and solved several complex crystal structures to gain insights into their binding mode. In addition, we present two structures of apo-MKK7, exhibiting a DFG-out and an unprecedented DFG-in/Leu-in conformation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
MAP Quinase Quinase 7
/
Inibidores de Proteínas Quinases
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article