Identification and Biological Evaluation of a Novel CLK4 Inhibitor Targeting Alternative Splicing in Pancreatic Cancer Using Structure-Based Virtual Screening.

ABSTRACT: Pancreatic cancer is an aggressive malignancy with a poor prognosis and limited treatment options. Cdc-like kinase 4 (CLK4), a kinase that regulates alternative splicing by phosphorylating spliceosome components, is implicated in aberrant splicing events driving pancreatic cancer progression. In this study, we established a computational model that integrates pharmacological interactions of CLK4 inhibitors with an improved hit rate. Through this model, we identified a novel CLK4 inhibitor, compound 150441, with a 50% inhibitory concentration (IC₅₀) value of 21.4 nm. Structure-activity relationship analysis was performed to investigate key interactions and functional groups. Kinase profiling revealed that compound 150441 is selective for CLK4. Subsequent in vitro assays demonstra

SUBMITTER: Yang CL 

PROVIDER: S-EPMC12097107 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature