Small molecule inhibitors of Stat3 signaling pathway

Constitutive activation of the Signal Transducers and Activators of Transcription 3 (Stat3) meditatedsignaling pathway is very important for cell growth and survival. Compelling evidence from mechanisticstudies with antisense, RNA interference (RNAi), peptides, and small molecular inhibitors indicate thatblocking Stat3 signaling can lead to successful suppression of tumor cell growth and apoptosis. Thus, Stat3 isan attractive molecular target for the development of novel cancer therapeutics. In this article, we present thefirst comprehensive review focusing on small molecule inhibitors that effectively block the Stat3 signalingpathway. These inhibitors, from a structural point of view, are divided into five classes of compounds. Theyinclude (1) natural products and derivatives, such as curcumin, resveratrol and others, (2) tyrphostins, (3)platinum-containing complexes, (4) peptidomimetics, and (5) azaspiranes. Some compounds may havemultiple targets including Stat3 protein, therefore these compounds need further optimization and validation.The purpose of this review is to provide a resource for researchers interested in Stat3 targeted small moleculeswhich will be beneficial for database development and template design for future drug development.