AC-3-019

AC-3-019 is a small molecule inhibitor of the Signal Transducer and Activator of Transcription 5 (STAT5) protein, specifically designed to target the SH2 domain. By binding to the SH2 domain, AC-3-019 disrupts the reciprocal STAT5-phosphopeptide interactions necessary for STAT5 phosphorylation, dimerization, nuclear translocation, and DNA binding. This inhibition effectively blocks STAT5-mediated gene transcription, which is a critical driver in hematopoietic malignancies such as acute myeloid leukemia (AML), particularly those harboring FLT3 internal tandem duplication (ITD) mutations. Developed through a collaboration involving the University of Toronto Mississauga and the Ludwig Boltzmann Institute for Cancer Research, AC-3-019 has demonstrated preclinical efficacy in suppressing tumor growth and inducing apoptosis in AML patient-derived samples without significant toxicity in healthy organs.