Structural Insights on the Role of Halogen Bonding in Protein MEK Kinase-Inhibitor Complexes.
Chem Asian J
; 19(7): e202301033, 2024 Apr 02.
Article
en En
| MEDLINE
| ID: mdl-38501888
ABSTRACT
Kinases are enzymes that play a critical role in governing essential biological processes. Due to their pivotal involvement in cancer cell signaling, they have become key targets in the development of anti-cancer drugs. Among these drugs, those containing the 2,4-dihalophenyl moiety demonstrated significant potential. Here we show how this moiety, particularly the 2-fluoro-4-iodophenyl one, is crucial for the structural stability of the formed drug-enzyme complexes. Crystallographic analysis of reported kinase-inhibitor complex structures highlights the role of the halogen bonding that this moiety forms with specific residues of the kinase binding site. This interaction is not limited to FDA-approved MEK inhibitors, but it is also relevant for other kinase inhibitors, indicating its broad relevance in the design of this class of drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteínas Quinasas
/
Antineoplásicos
Idioma:
En
Revista:
Chem Asian J
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Alemania