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Nature Reviews Drug Discovery 1, 696–709 (1 September 2002) | doi:10.1038/nrd895

Protein tyrosine phosphatase 1B inhibitors for diabetes

Theodore O. Johnson , Jacques Ermolieff & Michael R. Jirousek

Increased incidence of type 2 diabetes mellitus and obesity has elevated the medical need for new agents to treat these disease states. Resistance to the hormones insulin and leptin are hallmarks of both type 2 diabetes and obesity. Drugs that can ameliorate this resistance should be effective in treating type 2 diabetes and possibly obesity. Protein tyrosine phosphatase 1B (PTP1B) is thought to function as a negative regulator of insulin and leptin signal transduction. This article reviews PTP1B as a novel target for type 2 diabetes, and looks at the challenges in developing small-molecule inhibitors of this phosphatase.