Developing Inhibitors of STAT3: Targeting Downstream of the Kinases for Treating Disease

© 2015 Wiley-VCH Verlag GmbH & Co. KGaA,. All rights reserved. Over the past 20 years, drug discovery programs focusing on the aberrant disease-related proteins of the kinome have resulted in some of the most clinically significant small molecules. The enormous effort and success in producing potent inhibitors against these targets has laid the groundwork for more recent research into the design of inhibitors against more nontraditional targets of human disease. One protein of interest is the signal transducer and activator of transcription 3 (STAT3) that has been shown to play a central role in the progression of numerous diseases, including cancer, inflammatory disease and Alzheimer's disease, and is described as overactive in nearly 70% of all solid and hematological malignancies. This chapter first describes STAT3 structure and signaling and then focuses on directly targeting the STAT3 protein. Small molecules derived from natural sources are an important class of compounds to be utilized for the treatment of disease.