Structure-based discovery of new small molecule inhibitors of low molecular weight protein tyrosine phosphatase

The application of a fully integrated and automated virtual screening method for identifying potential and novel inhibitors of bovine lmwPTP is described. The protocol makes extensive use of our recently introduced LINGO tools, which allow the extraction of the implicit chemical information present in SMILES representations. Nine out of 34 compounds selected from a database of almost 500 000 commercially available compounds were experimentally confirmed to be competitive inhibitors of lmwPTP, two of them showing Ki values around 10 μM. The best inhibitors previously described had Ki values higher than 1 mM. These results constitute an experimental validation of our virtual screening algorithm and provide a basis for the optimization of pharmacologically interesting lmwPTP inhibitors.

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