Protein tyrosine phosphatase-based therapeutics: lessons from PTP1B

Abstract

The family of Protein Tyrosine Phosphatases (PTPs), which is encoded by ∼ 100 genes in humans, plays a critical role in the regulation of signal transduction. Recently a variety of links between aberrant PTP function and human disease have been defined and it has become apparent that generation of PTP inhibitors may present novel avenues for therapeutic intervention in several, major human diseases. The most clearly defined example is the potential of PTP1B as a target for treatment of diabetes and obesity. Nevertheless, it has also become apparent that the properties of the PTPs present significant challenges to drug development. In this review we focus on PTP1B. We describe its structure, catalytic mechanism and biological function, together with a review of the specialist literature that describes the generation of inhibitors of PTP1B. In doing so we have attempted to present an overview, aimed at those with a general interest in signal transduction, that illustrates both the progress that has been made and the challenges that are associated with the quest for PTP inhibitors as drugs.