Diphenylether Derivative as Selective Inhibitor of Protein Tyrosine Phosphatase 1B (PTP1B) Over T-cell Protein Tyrosine Phosphatase (TCPTP) Identified through Virtual Screening

Title:Diphenylether Derivative as Selective Inhibitor of Protein Tyrosine Phosphatase 1B (PTP1B) Over T-cell Protein Tyrosine Phosphatase (TCPTP) Identified through Virtual Screening

Volume: 13 Issue: 11

Author(s): M. V.V.V. Sekhar Reddy, Chakshusmathi Ghadiyaram, Sunil Kumar Panigrahi, Subramanya Hosahalli and Lakshmi Narasu Mangamoori

Affiliation:

Keywords: PTP1B, TCPTP, p-Nitro phenyl phosphate, Type II diabetes, Obesity.

Abstract: Even though protein tyrosine phosphatase has been identified as a validated therapeutic target over a decade for type II diabetes and obesity, developing a selective inhibitor to protein tyrosine phosphatase 1B (PTP1B) over other cellular PTPases has been a complicated task owing to the highly conserved and polar nature of the PTP1B catalytic site. Virtual screening study of in-house chemical depository resulted in the prioritization of few low molecular weight compounds as PTP1B inhibitors. The in-vitro pNPP assays were carried out on prioritized compounds in both PTP1B and T-cell protein tyrosine phosphatase (TCPTP). From this we identified four low molecular weight compounds as PTP1B inhibitors, of which the compound AU-2439 has shown 5 fold selectivity towards PTP1B over highly homologous TCPTP. In this short communication selectivity of AU-2439 is explained based on interaction with critical active site residues in both proteins using docking models.

Cite this article as:

Reddy V.V.V. Sekhar M., Ghadiyaram Chakshusmathi, Panigrahi Kumar Sunil, Hosahalli Subramanya and Mangamoori Narasu Lakshmi, Diphenylether Derivative as Selective Inhibitor of Protein Tyrosine Phosphatase 1B (PTP1B) Over T-cell Protein Tyrosine Phosphatase (TCPTP) Identified through Virtual Screening, Mini-Reviews in Medicinal Chemistry 2013; 13 (11) . https://dx.doi.org/10.2174/1389557511313110006