Chemical inhibitors targeting histone methylation readers.
Pharmacol Ther
; 256: 108614, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38401773
ABSTRACT
Histone methylation reader domains are protein modules that recognize specific histone methylation marks, such as methylated or unmethylated lysine or arginine residues on histones. These reader proteins play crucial roles in the epigenetic regulation of gene expression, chromatin structure, and DNA damage repair. Dysregulation of these proteins has been linked to various diseases, including cancer, neurodegenerative diseases, and developmental disorders. Therefore, targeting these proteins with chemical inhibitors has emerged as an attractive approach for therapeutic intervention, and significant progress has been made in this area. In this review, we will summarize the development of inhibitors targeting histone methylation readers, including MBT domains, chromodomains, Tudor domains, PWWP domains, PHD fingers, and WD40 repeat domains. For each domain, we will briefly discuss its identification and biological/biochemical functions, and then focus on the discovery of inhibitors tailored to target this domain, summarizing the property and potential application of most inhibitors. We will also discuss the structural basis for the potency and selectivity of these inhibitors, which will aid in further lead generation and optimization. Finally, we will also address the challenges and strategies involved in the development of these inhibitors. It should facilitate the rational design and development of novel chemical scaffolds and new targeting strategies for histone methylation reader domains with the help of this body of data.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Histonas
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Pharmacol Ther
Año:
2024
Tipo del documento:
Article