In silico identification of a novel Cdc2-like kinase 2 (CLK2) inhibitor in triple negative breast cancer.
Protein Sci
; 33(6): e5004, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38723164
ABSTRACT
Dysregulation of RNA splicing processes is intricately linked to tumorigenesis in various cancers, especially breast cancer. Cdc2-like kinase 2 (CLK2), an oncogenic RNA-splicing kinase pivotal in breast cancer, plays a significant role, particularly in the context of triple-negative breast cancer (TNBC), a subtype marked by substantial medical challenges due to its low survival rates. In this study, we employed a structure-based virtual screening (SBVS) method to identify potential CLK2 inhibitors with novel chemical structures for treating TNBC. Compound 670551 emerged as a novel CLK2 inhibitor with a 50% inhibitory concentration (IC50) value of 619.7 nM. Importantly, Compound 670551 exhibited high selectivity for CLK2 over other protein kinases. Functionally, this compound significantly reduced the survival and proliferation of TNBC cells. Results from a cell-based assay demonstrated that this inhibitor led to a decrease in RNA splicing proteins, such as SRSF4 and SRSF6, resulting in cell apoptosis. In summary, we identified a novel CLK2 inhibitor as a promising potential treatment for TNBC therapy.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Proteínas Serina-Treonina Quinases
/
Inibidores de Proteínas Quinases
/
Neoplasias de Mama Triplo Negativas
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article