Structure-based drug design of new leads for phosphatase research.

Biological targets that are challenging to pursue for medicinal chemists, such as the protein phosphatases, require creative and innovative approaches for identifying and optimizing previously unknown classes of inhibitors. To achieve these lofty objectives, medicinal chemists must utilize the latest computational, structural biology, synthetic and analytical technologies in the drug development process. The iterative use of structure-based drug design often plays a key role, as illustrated by the independent discoveries of two research groups involving the identification and optimization of protein tyrosine phosphatase 1B inhibitors that have novel heterocyclic phosphotyrosine mimetics. The newly designed pharmacophore provides a promising chemical lead for phosphatase drug discovery and a valuable chemical tool for phosphatase research in general.