Drug discovery and protein tyrosine phosphatases.

摘要: Protein tyrosine phosphatases (PTPs) play a critical role in physiological signaling pathways by controlling the level of phosphorylation. The past decade has seen vast increase both academic and industrial interest PTPs their relevance as potential therapeutic targets, with several PTP inhibitors recently entering clinical trials. Despite these developments, there are numerous examples failed drug discovery programs, such that have attained reputation `undruggable' targets. This review attempts to illustrate many obstacles must be overcome successfully develop drug, ranging from validation targets difficulties assessing true inhibitory nature apparently well-behaved compounds, along need balance physiocochemical properties required for active site binding characteristics needed vivo activity. A number structure-based design presented, cautionary tales inhibitor programs due unexpected shortcomings.