AI-10-49

AI-10-49 (also known as LeuSO) is a first-in-class, small-molecule protein-protein interaction (PPI) inhibitor that selectively targets the oncogenic fusion protein CBFβ-SMMHC (core binding factor β and smooth-muscle myosin heavy chain), which is expressed in acute myeloid leukemia (AML) patients harboring the chromosome inversion inv(16)(p13q22). Developed by the University of Virginia and licensed to Systems Oncology, AI-10-49 binds allosterically to the CBFβ portion of the fusion protein, disrupting its interaction with the tumor suppressor RUNX1. This disruption releases RUNX1, restoring its normal transcriptional activity and occupancy on target genes, which leads to the repression of oncogenic programs (such as MYC expression) and triggers apoptosis in inv(16)-positive leukemia cells. AI-10-49 is currently in preclinical development (IND-enabling studies) for the treatment of acute myeloid leukemia, and has also shown potential in preclinical research for triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC).

Brand names

LeuSO

Other names

AI1049AI-1049AI 1049