Screening a small hydrazide-hydrazone combinatorial library for targeting the STAT3 in monocyte-macrophages with insulated reporter transposons

Abstract The Signal Transducer and Activator of Transcription 3 (STAT3) pharmacological targeting is regarded as a prospective approach to treat cancer, autoimmune disorders, or inflammatory diseases. We have developed series reporters the STAT3, NF-κB, Nrf2, metal-responsive transcription factor-1 (MTF-1), hypoxia-inducible factor 1α (HIF-1α) transcriptional activation in human monocyte-macrophage line THP-1. reporter lines were employed test set hydrazide-hydrazones potential STAT3 inhibitors. A hydrazide-hydrazone library composed 70 binary combinations 7 carbonyl 10 hydrazide components, including inhibitor clinical drug nifuroxazide, has been assembled screened by reporters. For whole, significant correlations between responses NF-κB HIF-1α THP-1 monocytes found. selected inhibitory combinations, respective prepared tested individually. most potent 2-acetylpyridine 4-chlorobenzoylhydrazone exhibited significantly exceeding that nifuroxazide (ED 50 2 vs μM respectively) cells. conclude insulated transposons could be useful tool for discovery applications. Graphical