MC3138

MC3138 is a selective small molecule activator of Sirtuin 5 (SIRT5), a mitochondrial nicotinamide adenine dinucleotide (NAD+)-dependent enzyme that functions as a deacetylase, desuccinylase, and demalonylase. By activating SIRT5, MC3138 promotes the desuccinylation and subsequent inhibition of glutaminase (GLS), which leads to a reduction in glutamine metabolism—a key metabolic pathway for tumor growth. In preclinical studies involving triple-negative breast cancer (TNBC) models, MC3138 has been shown to decrease the expression of oncogenic markers such as HIF-1α and c-Myc, as well as the glutamine transporter SLC1A5. Its use results in the alteration of autophagy and mitophagy processes and triggers the toxic accumulation of mitochondrial reactive oxygen species (mtROS), ultimately inhibiting the growth of cancer spheroids.