AC-4-130

AC-4-130 is a small molecule inhibitor of Signal Transducer and Activator of Transcription 5 (STAT5), specifically targeting the SH2 domain. Developed through a collaboration involving the University of Toronto Mississauga and the Ludwig Boltzmann Institute for Cancer Research, it was designed to address hematopoietic malignancies such as acute myeloid leukemia (AML), particularly those harboring FLT3 internal tandem duplication (ITD) mutations. By binding to the STAT5 SH2 domain, AC-4-130 disrupts the reciprocal phosphopeptide interactions required for STAT5 phosphorylation, dimerization, nuclear translocation, and DNA binding. In preclinical models, the compound has demonstrated the ability to suppress tumor growth and induce apoptosis in AML cells, both as a monotherapy and in synergy with tyrosine kinase inhibitors or standard chemotherapy like cytarabine.