Discovery of a New CDK4/6 and PI3K/AKT Multiple Kinase Inhibitor Aminoquinol for the Treatment of Hepatocellular Carcinoma.

ABSTRACT: Background: Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC. Methods: Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were used to investigate whether the candidate dru

SUBMITTER: Xia ZK 

PROVIDER: S-EPMC8320333 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature