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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

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Therapeutic potential of targeting SHP2 in human developmental disorders and cancers

Dadong Shen1, Wenxia Chen2, Jinlin Zhu2

  • 1College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.

European Journal of Medicinal Chemistry
|February 17, 2020
PubMed

Insights

Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) plays a dual role in cancer, acting as both an oncoprotein and tumor suppressor. SHP2 inhibitors targeting its catalytic or allosteric sites are under development for cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is a key regulator of cellular processes.
  • SHP2 influences cell proliferation, differentiation, apoptosis, and survival by modulating signaling pathways like MAPK.
  • Aberrant SHP2 expression and mutations are linked to developmental disorders and various cancers.

Purpose of the Study:

  • To review the structure and biological function of SHP2.
  • To discuss the deregulation of SHP2 in human diseases.
  • To summarize recent advancements in SHP2 inhibitor development and their therapeutic potential.

Main Methods:

  • Literature review of SHP2 structure, function, and disease association.
  • Summary of current SHP2 inhibitor development strategies.
  • Analysis of SHP2's dual role in oncogenesis and tumor suppression.

Main Results:

  • SHP2's complex role in cancer, acting as both an oncoprotein and tumor suppressor depending on the context.
  • Development of two classes of SHP2 inhibitors: catalytic site and allosteric inhibitors.
  • Resolved cocrystal structures provide insights into inhibitor binding and mechanism.

Conclusions:

  • SHP2 is a promising therapeutic target in oncology due to its critical role in cancer signaling.
  • Context-specific roles of SHP2 necessitate tailored therapeutic strategies.
  • Ongoing development of SHP2 inhibitors holds significant potential for cancer treatment.
Keywords:
Allosteric siteCancerCatalytic pocketDevelopmental disorderSHP2 inhibitor

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