Article: CD38 Inhibitor MK-0159 Preserves NAD+ and Protects the Heart From Ischemia/Reperfusion Injury: Preclinical Findings

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Cardiovascular Disease Cardiovascular Health Preclinical

CD38 Inhibitor MK-0159 Preserves NAD+ and Protects the Heart From Ischemia/Reperfusion Injury: Preclinical Findings

Synopsis

The enzyme CD38 breaks down important molecules like NAD+ and NADP+, which are vital for cellular energy production and mitochondrial health. When CD38 activity increases—such as during aging, inflammation, or heart injury—it depletes NAD+ and NADP+, leading to cell damage and impaired heart function. In this study, researchers developed a new CD38 inhibitor called MK-0159, which blocks the enzyme with very high potency. In mice, MK-0159 provided stronger protection against heart damage after ischemia/reperfusion (I/R) injury than both nicotinamide riboside (NR)—a vitamin B3–derived NAD+ booster—and an older CD38 inhibitor. These results suggest that directly blocking CD38 activity may be a more powerful strategy than boosting NAD+ levels alone for preventing heart tissue damage and improving recovery after cardiac injury.

Journal

Journal of Medicinal Chemistry

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