Open AccessA Profiling Platform for the Identification of Selective Metalloprotease Inhibitors
Author(s) -
Christophe Antczak,
Constantin Radu,
Hakim Djaballah
Publication year - 2008
Publication title -
slas discovery
Language(s) - English
Resource type - Journals
eISSN - 2472-5560
pISSN - 2472-5552
DOI - 10.1177/1087057108315877
Subject(s) - profiling (computer programming) , proteases , computational biology , chemistry , metalloproteinase , drug discovery , selectivity , homogeneous , combinatorial chemistry , biochemistry , enzyme , biology , computer science , physics , thermodynamics , catalysis , operating system
Although proteases represent an estimated 5% to 10% of potential drug targets, inhibitors for metalloproteases (MPs) account for only a small proportion of all approved drugs, failures of which have typically been associated with lack of selectivity. In this study, the authors describe a novel and universal binding assay based on an actinonin derivative and show its binding activities for several MPs and its lack of activity toward all the non-MPs tested. This newly developed assay would allow for the rapid screening for inhibitors of a given MP and for the selectivity profiling of the resulting hits. The assay has successfully enabled for the first time simultaneous profiling of 8 well-known inhibitors against a panel of selected MPs. Previously published activities for these inhibitors were confirmed, and the authors have also discovered new molecular targets for some of them. The authors conclude that their profiling platform provides a generic assay solution for the identification of novel metalloprotease inhibitors as well as their selectivity profiling using a simple and homogeneous assay.