Specificity of Poly(ADP-Ribose) Synthetase Inhibitors

Abstract

Poly(ADP-ribose) synthetase inhibitors, and in particular 3-aminobenzamide, have been used extensively in recent years as probes to elucidate the function of poly(ADP-ribose) in the cell. Our initial report [1] on substituted benzamides as physiologically specific inhibitors was based on the observation that cells grew at an unchanged rate in the presence of 2 mM 3-aminobenzamide, a concentration 1,000 times the K_i value. In general, high concentrations are needed to elicit a cellular response compared to assays in vitro. Interpretation of results is complicated by the possibility of affecting a target other than poly(ADP-ribose) synthetase. Recently, processes other than ADP-ribosylation have been reported to be altered by benzamides. A major criticism of most work is that the studies entail the use of only one inhibitor, usually 3-aminobenzamide.