Stemcell, 73652, EX527

EX527 is a cell-permeable, selective inhibitor of mammalian sirtuin 1 (SIRT1; IC₅₀ = 98 nM) over SIRT2 and SIRT3 and has no effect on other histone deacetylases (HDACs; Nayagam et al.). SIRT1 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase with roles in energy metabolism and inflammation. Studies have shown that EX527 inhibits sirtuins by forming a trimeric sirtuin complex with an NAD+-derived coproduct (Gertz M et al.).

DIFFERENTIATION

· Increases the production of oligodendrocytes from differentiating neural stem cells and neural progenitor cells in vitro (Rafalski et al.).

IMMUNOLOGY

· Restores the microvascular response during the hypoinflammatory phase in a mouse model of sepsis, and enhances the systemic innate immune response (Vachharajani et al.).

DISEASE MODELING

· Delays cyst growth in kidneys of PKD1 knockout mouse models (Zhou et al.)