Bioorthogonal Probes for the Study of MDM2-p53 Inhibitors in Cells and Development of High-Content Screening Assays for Drug Discovery.
Angew Chem Int Ed Engl
; 55(52): 16026-16030, 2016 12 23.
Article
en En
| MEDLINE
| ID: mdl-27874234
ABSTRACT
To study the behavior of MDM2-p53 inhibitors in a disease-relevant cellular model, we have developed and validated a set of bioorthogonal probes that can be fluorescently labeled in cells and used in high-content screening assays. By using automated image analysis with single-cell resolution, we could visualize the intracellular target binding of compounds by co-localization and quantify target upregulation upon MDM2-p53 inhibition in an osteosarcoma model. Additionally, we developed a high-throughput assay to quantify target occupancy of non-tagged MDM2-p53 inhibitors by competition and to identify novel chemical matter. This approach could be expanded to other targets for lead discovery applications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteosarcoma
/
Proteína p53 Supresora de Tumor
/
Evaluación Preclínica de Medicamentos
/
Proteínas Proto-Oncogénicas c-mdm2
/
Colorantes Fluorescentes
/
Indoles
/
Antineoplásicos
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2016
Tipo del documento:
Article
País de afiliación:
Suiza