Targeting protein tyrosine phosphatase to enhance insulin action for the potential treatment of diabetes.

The increasing prevalence of type 2 diabetes has sparked interest in the development of agents that treat and prevent the disease. Mounting evidence indicates that protein tyrosine phosphatase (PTP)1B negatively regulates insulin and leptin signaling making it a prime target for enhancing insulin sensitivity and controlling body mass. Despite intense efforts, development of orally bioavailable small-molecule PTP1B inhibitors has been a challenge. This review focuses on recent advances in the validation of PTP1B and in the development of approaches to modulate its activity.