title: Small molecule inhibitors of Stat3 signaling pathway.
abstract: Constitutive activation of the Signal Transducers and Activators of Transcription 3 (Stat3) meditated signaling pathway is very important for cell growth and survival. Compelling evidence from mechanistic studies with antisense, RNA interference (RNAi), peptides, and small molecular inhibitors indicate that blocking Stat3 signaling can lead to successful suppression of tumor cell growth and apoptosis. Thus, Stat3 is an attractive molecular target for the development of novel cancer therapeutics. In this article, we present the first comprehensive review focusing on small molecule inhibitors that effectively block the Stat3 signaling pathway. These inhibitors, from a structural point of view, are divided into five classes of compounds. They include (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 have multiple 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 molecules which will be beneficial for database development and template design for future drug development.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Deng
authors.forename: Fedora
authors.initials: F
authors.lastname: Grande
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology; D005419:Flavonoids; D006801:Humans; D010880:Piperidines; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D014315:Triterpenes; C041246:cucurbitacin B; C077990:alvocidib; D003474:Curcumin; D000077185:Resveratrol