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.
