Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors

Inhibition of the signaling pathways of signal transducer and activator of transcription 3 (STAT 3) has shown to be a promising strategy to combat cancer. In this paper we report the design, synthesis and evaluation of a novel class of small molecule inhibitors, that is, XZH-5 and its analogues, as promising leads for further development of STAT3 inhibitors. Preliminary SARs was established for XZH-5 and its derivatives; and the binding modes were predicted by molecular docking. Lead compounds with IC50 as low as 6.5 mu M in breast cancer cell lines and 7.6 mu M in pancreatic cancer cell lines were identified. (C) 2015 Elsevier Ltd. All rights reserved.