Targeting PTPs with small molecule inhibitors in cancer treatment

Zhong Xing Jiang, Zhong-Yin Zhang

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Protein tyrosine phosphorylation plays a major role in cellular signaling. The level of tyrosine phosphorylation is controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Disturbance of the normal balance between PTK and PTP activity results in aberrant tyrosine phosphorylation, which has been linked to the etiology of several human diseases, including cancer. A number of PTPs have been implicated in oncogenesis and tumor progression and therefore are potential drug targets for cancer chemotherapy. These include PTP1B, which may augment signaling downstream of HER2/Neu; SHP2, which is the first oncogene in the PTP superfamily and is essential for growth factor-mediated signaling; the Cdc25 phosphatases, which are positive regulators of cell cycle progression; and the phosphatase of regenerating liver (PRL) phosphatases, which promote tumor metastases. As PTPs have emerged as drug targets for cancer, a number of strategies are currently been explored for the identification of various classes of PTP inhibitors. These efforts have resulted many potent, and in some cases selective, inhibitors for PTP1B, SHP2, Cdc25 and PRL phosphatases. Structural information derived from these compounds serves as a solid foundation upon which novel anti-cancer agents targeted to these PTPs can be developed.

Original languageEnglish
Pages (from-to)263-272
Number of pages10
JournalCancer and Metastasis Reviews
Volume27
Issue number2
DOIs
StatePublished - Jun 2008

Fingerprint

Protein Tyrosine Phosphatases
cdc25 Phosphatases
Phosphoric Monoester Hydrolases
Neoplasms
Tyrosine
Phosphorylation
Protein-Tyrosine Kinases
Therapeutics
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Liver
Oncogene Proteins
Pharmaceutical Preparations
Intercellular Signaling Peptides and Proteins
Cell Cycle
Carcinogenesis
Neoplasm Metastasis
Drug Therapy

Keywords

  • Cdc25
  • PRL phosphatases
  • Protein tyrosine phosphatase (PTP)
  • PTP inhibitor
  • PTP1B
  • SHP2
  • Small molecule inhibitor design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Targeting PTPs with small molecule inhibitors in cancer treatment. / Jiang, Zhong Xing; Zhang, Zhong-Yin.

In: Cancer and Metastasis Reviews, Vol. 27, No. 2, 06.2008, p. 263-272.

Research output: Contribution to journalArticle

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