Discovery of PARP1-Sparing Inhibitors for Protein ADP-Ribosylation

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Nov 20

PMID 39563804

Authors

Elisa N Stephens

Liang-Chieh Chen

Arshad J Ansari

Kaiyu Shen

Lei Zhang

Steven G Guillen

Clay C C Wang

Yong Zhang

Affiliations

Soon will be listed here.

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.

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