Targeting Acute Myeloid Leukemia through Multi-Functional Small Molecules: Insights from Cheminformatics and Mitochondrial Modulation

Highlight

• Novel PS127-family compounds identified via cheminformatic screening exhibit selective cytotoxicity against AML through combined induction of apoptosis, autophagy, and glutathione reductase inhibition.
• These compounds provoke mitochondrial dysfunction characterized by increased reactive oxygen species (ROS), decreased oxygen consumption, and reduced ATP synthesis.
• The compounds demonstrate synergistic anti-leukemic effects with standard therapeutic agents midostaurin, venetoclax, and doxorubicin, validated in both AML cell lines and patient-derived primary cells.
• Cheminformatics-based function prediction successfully guided identification of structurally diverse molecules with consistent AML-targeting phenotypes, underscoring translational potential.

Study Background