Small molecule targeting of PTPs in cancer

Int J Biochem Cell Biol. 2018 Mar:96:171-181. doi: 10.1016/j.biocel.2017.09.011. Epub 2017 Sep 21.

Abstract

Protein tyrosine phosphatases (PTPs) undeniably have a central role in the development and progression of human cancers. Historically, however, PTPs have not been viewed as privileged drug targets, and progress on identifying potent, selective, and cell-active small molecule PTP inhibitors has suffered accordingly. This situation is rapidly changing, however, due to biochemical advances in the study of PTPs and recent small molecule screening campaigns, which have identified potent and mechanistically diverse lead structures. These compounds are facilitating the exploration of the fundamental cellular processes controlled by PTPs in cancers, and could form the inflection point for new therapeutic paradigms for the treatment of a range of cancers. Herein, we review recent advances in the discovery and biological annotation of cancer-relevant small molecule PTP inhibitors.

Keywords: Allosteric inhibition; Cancer; Chemical probes; Drug-like inhibitors; Tyrosine phosphatases.

Publication types

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

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / therapeutic use
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / enzymology
  • Neoplasms* / genetics
  • Protein Tyrosine Phosphatases* / antagonists & inhibitors
  • Protein Tyrosine Phosphatases* / genetics
  • Protein Tyrosine Phosphatases* / metabolism

Substances

  • Enzyme Inhibitors
  • Protein Tyrosine Phosphatases