On the mechanism of action of SJ-172550 in inhibiting the interaction of MDM4 and p53.
PLoS One
; 7(6): e37518, 2012.
Article
en En
| MEDLINE
| ID: mdl-22675482
SJ-172550 (1) was previously discovered in a biochemical high throughput screen for inhibitors of the interaction of MDMX and p53 and characterized as a reversible inhibitor (J. Biol. Chem. 2010; 285:10786). Further study of the biochemical mode of action of 1 has shown that it acts through a complicated mechanism in which the compound forms a covalent but reversible complex with MDMX and locks MDMX into a conformation that is unable to bind p53. The relative stability of this complex is influenced by many factors including the reducing potential of the media, the presence of aggregates, and other factors that influence the conformational stability of the protein. This complex mechanism of action hinders the further development of compound 1 as a selective MDMX inhibitor.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Proteínas Nucleares
/
Proteína p53 Supresora de Tumor
/
Proteínas Proto-Oncogénicas
/
Acetatos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos