Targeting protein-protein interaction by small molecules.
Annu Rev Pharmacol Toxicol
; 54: 435-56, 2014.
Article
en En
| MEDLINE
| ID: mdl-24160698
ABSTRACT
Protein-protein interactions (PPIs) are critical regulatory events in physiology and pathology, and they represent an important target space for pharmacological intervention. However, targeting PPIs with small molecules is challenging owing to the large surface area involved in protein-protein binding and the lack of obvious small-molecule-binding pockets at many protein-protein interfaces. Nonetheless, successful examples of small-molecule modulators of PPIs have been growing in recent years. This article reviews some of the recent advances in the discovery of small-molecule regulators of PPIs that involve key oncogenic proteins. Our discussion focuses on the three key modes of action for these small-molecule modulators orthosteric inhibition, allosteric regulation, and interfacial binding/stabilization. Understanding the opportunities and challenges of these diverse mechanisms will help guide future efforts in developing small-molecule modulators against PPIs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dominios y Motivos de Interacción de Proteínas
/
Terapia Molecular Dirigida
Tipo de estudio:
Qualitative_research
Límite:
Humans
Idioma:
En
Revista:
Annu Rev Pharmacol Toxicol
Año:
2014
Tipo del documento:
Article