Issues

There is an unmet medical need for pharmacological inhibitors of signal transducer and activator of transcription 5a/b (Stat5a/b). Stat5a/b is critical for growth and progression of solid tumors and hematological malignancies, specifically prostate cancer and Bcr-Abl–driven leukemias. IST5-002, a lead compound of a small molecule inhibitor family of Stat5a/b, was identified through structure-based in-silico screening and medicinal chemistry. IST5-002 potently inhibited molecular events associated with Stat5a/b activation, reduced the expression of Stat5a/b-regulated genes and induced extensive apoptotic cell death in multiple models of prostate cancer and chronic myeloid leukemias in vitro, in vivo, and in patient samples. IST5-002 provides a lead structure for further chemical modifications for clinical development. For details, see article by Liao et al., on page 1777.