Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase.
@article{Babaoglu2008ComprehensiveMA, title={Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase.}, author={Kerim Babaoglu and Anton Simeonov and John J. Irwin and Michael E. Nelson and Brian Y Feng and Craig J. Thomas and Laura Cancian and Maria Paola Costi and David A. Maltby and Ajit Jadhav and James Inglese and Christopher P. Austin and Brian K. Shoichet}, journal={Journal of medicinal chemistry}, year={2008}, volume={51 8}, pages={ 2502-11 } }
High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate "hit lists"; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against beta-lactamase using quantitative HTS (qHTS). Of the 1,274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting beta…
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