University of Toronto
Preclinical development of an anti-AML small molecule, JP-4-94
Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults. Worldwide, AML affects forty individuals per million annually. The majority of AML patients respond to toxic chemotherapy initially, but due to therapy resistant relapses, the 5-year overall survival is below 50%, and below 20% for patients >60 years. There is an intense medical need for new therapeutic options. Furthermore, demographic change and improved medical care will lead to more AML cases in the future. For example, many current chemotherapeutic interventions promote AML. The major hurdle in identifying an effective AML drug, is that it must be capable of entering blood producing organs like bone marrow to efficiently kill leukemic cells. We have developed a molecule which targets STAT5, an important driver of blood cancers. The compound exhibits potent killing of AML cells while not killing normal cells at same concentrations, is orally bioavailable, and most importantly, penetrates bone marrow and other blood producing organs. We seek to optimize the drug structurally, identify mechanism of action against STAT5, and conduct preclinical trials in animal models of AML to identify an advanced preclinical candidate for treatment of AML.