Format

Send to

Choose Destination
ACS Chem Biol. 2013 Aug 16;8(8):1698-703. doi: 10.1021/cb4002014. Epub 2013 Jun 25.

PARP inhibitor with selectivity toward ADP-ribosyltransferase ARTD3/PARP3.

Author information

1
Department of Chemistry, Umeå University, Umeå, Sweden.

Abstract

Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12 members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.

PMID:
23742272
DOI:
10.1021/cb4002014
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center