Rational Design of Cell-Active Inhibitors of PARP10.

ABSTRACT: Poly-ADP-ribose polymerases (PARPs 1-16) have emerged as major regulators of diverse cellular processes. PARPs can be subclassified based on their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). While much is known about the cellular roles of PARPs that catalyze PARylation (e.g., PARP1), the function of PARPs that catalyze MARylation (e.g., PARP10) is substantially less understood. This is due in large part to the lack of small-molecule inhibitors that are selective for individual PARP family members that catalyze MARylation. Herein, we describe the rational design and synthesis of selective inhibitors of PARP10. Using structure-based design, we targeted a hydrophobic subpocket within the nicotinamide-binding site of PARP10. We synthesized a se

SUBMITTER: Morgan RK 

PROVIDER: S-EPMC6331153 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature