Introduction: The clinical utility of effective direct STAT inhibitors, particularly STAT3 and STAT5, for treating cancer and other diseases is well studied and known.
Areas covered: This review will highlight the STAT inhibitor patent literature from 2011 to 2015 inclusive. Emphasis will be placed on inhibitors of the STAT3, STAT5a/b, and STAT1 proteins for cancer treatment. The review will, where suitably investigated, describe the mode and the site of inhibition, list indications that were evaluated, and rank the inhibitor's relative potency among compounds in the same class. The reader will gain an understanding of the diverse set of approaches, used both in academia and industry, to target STAT proteins.
Expert opinion: There is still much work to be done to directly target the STAT3 and STAT5 proteins. As yet, there is still no direct STAT3 inhibitor in the clinic. While the SH2 domain remains a popular target for therapeutic intervention, the DNA-binding domain and N-terminal region are now attracting attention as possible sites for inhibition. Multiple putative STAT3 and STAT5 inhibitors have now been patented across a broad spectrum of chemotypes, each with their own advantages and limitations.
Keywords: JAK/STAT pathway; anti-cancer drugs; cancer therapeutics; molecular therapeutics; oncogene; protein–protein interactions; signal transducer and activator of transcription 3 (STAT3).