Integrating virtual and biochemical screening for protein tyrosine phosphatase inhibitor discovery

Katie R. Martin, Pooja Narang, José L. Medina-Franco, Nathalie Meurice, Jeffrey P. MacKeigan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Protein tyrosine phosphatases (PTPs) represent an important class of enzymes that mediate signal transduction and control diverse aspects of cell behavior. The importance of their activity is exemplified by their significant contribution to disease etiology with over half of all human PTP genes implicated in at least one disease. Small molecule inhibitors targeting individual PTPs are important biological tools, and are needed to fully characterize the function of these enzymes. Moreover, potent and selective PTP inhibitors hold the promise to transform the treatment of many diseases. While numerous methods exist to develop PTP-directed small molecules, we have found that complimentary use of both virtual (in silico) and biochemical (in vitro) screening approaches expedite compound identification and drug development. Here, we summarize methods pertinent to our work and others. Focusing on specific challenges and successes we have experienced, we discuss the considerable caution that must be taken to avoid enrichment of inhibitors that function by non-selective oxidation. We also discuss the utility of using "open" PTP structures to identify active-site directed compounds, a rather unconventional choice for virtual screening. When integrated closely, virtual and biochemical screening can be used in a productive workflow to identify small molecules targeting PTPs.

Original languageEnglish (US)
Pages (from-to)219-228
Number of pages10
Issue number2
StatePublished - Jan 15 2014


  • Inhibitor
  • PTP
  • PTPσ
  • Protein tyrosine phosphatase
  • Small molecule
  • Virtual screen

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology


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