Abstract
Protein tyrosine phosphatase1B (PTP1B), a significant negative regulator in insulin and leptin signaling pathways, has emerged as a promising drug target for Type II diabetes mellitus and obesity. Numerous potent PTP1B inhibitors have been discovered within both academia and pharmaceutical industry. However, nearly all medicinal chemistry efforts have been severely hindered because a vast majority of them demonstrate poor membrane permeability and low-selectivity, especially over T-cell protein tyrosine phosphatase (TCPTP). To search the rules about the selectivity over TCPTP and membrane permeability of PTP1B inhibitors, based on the PTP1B/inhibitor crystal complexes, the development PTP1B inhibitors defined as AB, AC, ABC and ADC types have been concluded in the review.
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