NRD167

NRD167 is a novel small molecule inhibitor of Sirtuin 5 (SIRT5), a mitochondrial enzyme that possesses unique desuccinylase, demalonylase, and deglutarylase activities. Identified through research at the University of Utah and other institutions, NRD167 targets the metabolic dependencies of acute myeloid leukemia (AML) cells. SIRT5 is critical for maintaining redox homeostasis and metabolic flux in AML, particularly regulating glutamine metabolism and oxidative phosphorylation (OXPHOS). Preclinical studies have demonstrated that NRD167 treatment reduces cell proliferation, induces apoptosis, and impairs mitochondrial function in SIRT5-dependent AML cell lines and patient-derived samples, while sparing normal hematopoietic cells. This selective dependency suggests SIRT5 as a viable therapeutic target in AML.