AP-3

AP-3 is a highly potent natural compound identified through high-throughput screening as a potential therapeutic for T-cell acute lymphoblastic leukemia (T-ALL). It exerts its anti-leukemic effects by directly binding to the MORF4L1-associated protein (MRGBP), a component of the NuA4/Tip60 histone acetyltransferase complex. This binding leads to the downregulation of the Tip60/MYC signaling axis, which subsequently induces apoptosis and M phase cell cycle arrest in T-ALL cells. Notably, AP-3's mechanism of action is independent of the Notch1 pathway, a common driver of T-ALL, suggesting its potential utility in Notch1-independent disease subtypes. Preclinical studies in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models have demonstrated that AP-3 significantly reduces tumor burden and prolongs survival.