In silico and in vitro identification of inhibitory activities of sorafenib on histone deacetylases in hepatocellular carcinoma cells.

ABSTRACT: Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles. In vitro experimental analyses demonstrated that sorafenib indirectly inhibited HDAC activity in both sorafenib-sensitive and -resistant HCC cells. A cancer genomics analysis using th

SUBMITTER: Liu TP 

PROVIDER: S-EPMC5689675 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature