Design, Synthesis and Biological Evaluation of Noncovalent Inhibitors of Human CD38 NADase

Shoot the messenger! CD38 is a multifunctional enzyme responsible for the generation of calcium ion messengers. A structural optimization was carried out to develop noncovalent CD38 inhibitors based on hit compound S125 (top) (IC50=86 μM). The best compound inhibited CD38 NADase with an IC50 value of 4.7 μM (bottom). Molecular modeling was used to predict potentially important interactions between the inhibitor and enzyme.