MK-0159

MK-0159 is a potent, selective, and orally active small molecule enzymatic inhibitor of CD38 (ADP-ribosyl cyclase 1). It was developed by Mitobridge (a wholly owned subsidiary of Astellas Pharma). CD38 is a major nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) consuming enzyme in mammals, and its upregulation is associated with age-related inflammation, metabolic diseases, and ischemia/reperfusion (I/R) injury. By inhibiting CD38, MK-0159 prevents the depletion of NAD+ and NADP+, thereby restoring intracellular NAD+ homeostasis, improving mitochondrial fitness, and protecting tissues from oxidative stress and damage. Preclinical studies have demonstrated its therapeutic potential in ameliorating myocardial damage following cardiac ischemia/reperfusion injury, as well as reversing mitochondrial defects and restoring T-cell function in models of systemic lupus erythematosus (SLE).