Discovery of PARP1-Sparing Inhibitors for Protein ADP-Ribosylation.

ABSTRACT: Poly-ADP-ribose polymerases (PARPs) that catalyze cellular ADP-ribosylation play important roles in human health. PARP inhibitors have found success in the clinic for cancer treatment. However, isoform-specific inhibitors are needed for improved safety. Here, we report the unexpected discovery of nicotinamide mimics that block non-PARP1-catalyzed ADP-ribosylation at micromolar concentrations. These PARP1-sparing PARP inhibitors represent first-in-class probes for ADP-ribosylation, shedding light on the selective inhibition of PARPs.

SUBMITTER: Stephens EN 

PROVIDER: S-EPMC11571001 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature