Targeting Tyrosine Phosphatases: Time to End the Stigma

Trends Pharmacol Sci. 2017 Jun;38(6):524-540. doi: 10.1016/ Epub 2017 Apr 12.


Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, and several PTPs have been validated as therapeutic targets for human diseases. Historically, the development of drugs targeting PTPs has been highly challenging, leading to stigmatization of these enzymes as undruggable targets. Despite these difficulties, efforts to drug PTPs have persisted, and recent years have seen an influx of new probes providing opportunities for biological examination of old and new PTP targets. Here we discuss progress towards drugging PTPs with special emphasis on the development of selective probes with biological activity. We describe the development of new small-molecule orthosteric, allosteric, and oligomerization-inhibiting PTP inhibitors and discuss new studies targeting the receptor PTP (RPTP) subfamily with biologics.

Keywords: allosteric; biologic; drug target; inhibitor; protein tyrosine phosphatase; small molecule.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Targeted Therapy
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Protein Tyrosine Phosphatases / metabolism
  • Small Molecule Libraries / pharmacology


  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Protein Tyrosine Phosphatases