Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Proteinâ
A.
ChemMedChem
; 11(8): 893-9, 2016 Apr 19.
Article
en En
| MEDLINE
| ID: mdl-26748787
ABSTRACT
Replication proteinâ
A (RPA) is an essential single-stranded DNA (ssDNA)-binding protein that initiates the DNA damage response pathway through protein-protein interactions (PPIs) mediated by its 70N domain. The identification and use of chemical probes that can specifically disrupt these interactions is important for validating RPA as a cancer target. A high-throughput screen (HTS) to identify new chemical entities was conducted, and 90 hit compounds were identified. From these initial hits, an anthranilic acid based series was optimized by using a structure-guided iterative medicinal chemistry approach to yield a cell-penetrant compound that binds to RPA70N with an affinity of 812â
nm. This compound, 2-(3- (N-(3,4-dichlorophenyl)sulfamoyl)-4-methylbenzamido)benzoic acid (20 c), is capable of inhibiting PPIs mediated by this domain.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína de Replicación A
/
Ortoaminobenzoatos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Año:
2016
Tipo del documento:
Article