YC8-02

YC8-02 is a selective small molecule inhibitor of Sirtuin 3 (SIRT3), a mitochondrial NAD+-dependent deacetylase. Developed by researchers at Cornell University, YC8-02 targets the metabolic dependency of certain cancers on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). In preclinical models of acute myeloid leukemia (AML) and B-cell lymphoma, YC8-02 treatment leads to the accumulation of long-chain fatty acids, a reduction in tricarboxylic acid (TCA) cycle intermediates, and a significant decrease in basal oxygen consumption and ATP production. This metabolic disruption selectively induces cell death in leukemic stem cells (LSCs) while sparing normal hematopoietic cells, suggesting SIRT3 as a viable therapeutic target for eliminating disease-initiating cells in AML.