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From the initial PTP studies in the early 1980s (Nelson and Branton 1984; Sparks and Brautigan 1986), to the successful purification of PTP1B (Tonks et al. 1988a,b), we have gathered an impressive knowledge on the enzymatic properties and structure of PTPs. The realization that PTP1B could potentially be an outstanding target for diabetes and obesity has launched a broad search for pharmacological inhibitors. For the past 5 years this search revealed several difficulties in finding the optimal compounds. In spite of the difficult chemistry, one may hope that these efforts will continue. As this review entails to show, a great number of other targets await the first success with PTP1B. Once an optimal compound for PTP1B is found, it would be much easier to model such a chemical(s) to the other very closely related members of the family (Andersen et al. 2001). Overall, it is clear that the PTP family holds great promise for the treatment of several human diseases, and we only need the chemistry to catch up with the outstanding biology that has been recently revealed on many of the PTP family members.


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