Development of Tyrosine Phosphatase 1B Inhibitors Based on Molecular Docking, Kinetics, and Toxicity Studies.

Protein Tyrosine Phosphatase 1B (PTP1B) is a protein that contributes to the development of diseases that affect millions of people worldwide. In the last five years, several studies have been carried out to develop a drug that is capable of inhibiting the functions of this protein that are related to chronic degenerative diseases and obesity. In this study, we used PTP1B as a therapeutic target to perform a molecular docking to identify compounds that specifically bind to the PTP1B human protein. After molecular docking from over 500,000 compounds, we selected the six with the highest binding score and evaluated their inhibitory effect in in vitro assays. The data showed that PT2 compound was the most potent with an IC50 value of 9 μM and a noncompetitive inhibition mechanism. According to molecular docking, this compound made specific interactions in the catalytic domain of PTP1B, that could be responsible for their inhibition capability. Furthermore, cytotoxic studies in MCF‐7 cells indicated that it could be safe for humans. Therefore, PT2 compound may be a promising new drug to attend the diseases where PTP1B has functions. [ABSTRACT FROM AUTHOR]