Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

PARP Inhibitors

  • Manfred Schwab
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_4395-2

Definition

Poly(ADP-ribose) polymerase inhibitors are a large number of low molecular weight compounds (NAD+ analogues) that competitively inhibit PARP activity. Among the first to be described were nicotinamide, benzamide, and 3-aminobenzamide. However, their potency and specificity is rather low. Subsequently, more sophisticated new compounds have been developed such as 4-amino-1,8-naphthalimide, 3,4-dihydro-5-methoxyisoquinolin-1(2H)-one (PD 128763), 8-hydroxy-2-methylquinazolin-4(3H)-one (NU1025), or 2-methylbenzimidazole-4-carboxamide (NU1064), to name but a few. These are much more potent than the first-generation inhibitors and possess an improved pharmacokinetic profile.

With respect to specificity, while all inhibitors inhibit PARP-1 (by definition), at least some of the first-generation inhibitors also interfered with other ADP-ribosyl transfer reactions, such as mono-ADP-ribosylation of proteins or NAD+ glycohydrolases, albeit at different IC50 levels. Furthermore, the novel...

Keywords

Molecular Weight Cancer Research Transfer Reaction Pharmacokinetic Profile PARP Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.German Cancer Research Center (DKFZ)HeidelbergGermany