Diphenylether derivative as selective inhibitor of protein tyrosine phosphatase 1B (PTP1B) over T-cell protein tyrosine phosphatase (TCPTP) identified through virtual screening

M. V V V Sekhar Reddy, Chakshusmathi Ghadiyaram, Sunil Kumar Panigrahi, Subramanya Hosahalli, Lakshmi Narasu Mangamoori

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1602-1606
Number of pages5
JournalMini-Reviews in Medicinal Chemistry
Volume13
Issue number11
StatePublished - 2013
Externally publishedYes

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Keywords

  • Obesity
  • p-Nitro phenyl phosphate
  • PTP1B
  • TCPTP
  • Type II diabetes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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