Mechanism of action of selective inhibitors of IL-6 induced STAT3 pathway in head and neck cancer cell lines.

ABSTRACT: Studies indicate that elevated interleukin-6 (IL-6) levels engage IL6Rα-gp130 receptor complexes to activate signal transducer and activator of transcription 3 (STAT3) that is hyperactivated in many cancers including head and neck squamous cell carcinoma (HNSCC). Our previous HCS campaign identified several hits that selectively blocked IL-6-induced STAT3 activation. This study describes our investigation of the mechanism(s) of action of three of the four chemical series that progressed to lead activities: a triazolothiadiazine (864669), amino alcohol (856350), and an oxazole-piperazine (4248543). We demonstrated that all three blocked IL-6-induced upregulation of the cyclin D1 and Bcl-X_L STAT3 target genes. None of the compounds exhibited direct binding interactions with STAT3

SUBMITTER: Sen M 

PROVIDER: S-EPMC5480263 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature