Prospects for Clinical Development of Stat5 Inhibitor IST5-002: High Transcriptomic Specificity in Prostate Cancer and Low Toxicity In Vivo

摘要

There is an unmet medical need for new and potent pharmacological inhibitor drugs for the protein Stat5 that would be orally bioavailable for treatment of several different cancers. Previous work has established a critical role for Stat5 in molecular and clinical progression of prostate cancer to metastatic disease and in the pathogenesis of several leukemias and blood-based disorders. Our group has developed a potent pharmacological inhibitor for Stat5, IST5-002, which targets two critical steps in the activation process of Stat5 in cancer cells. In the present work, we evaluated the characteristics of IST5-002 for further development into a cancer drug. We evaluated whether IST5-002 affects the Stat5 targets genes in prostate cancer, defined more closely its mechanisms of action, and investigated its initial toxicity as the basis for further development in order to enable its entrance into clinical testing in patients. Our study supports optimization of IST5-002 compound for oral bioavailability and for clinical development.