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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Progress towards the development of SH2 domain inhibitors
Dziyana Kraskouskaya1, Eugenia Duodu, Carolynn C Arpin
1Department of Chemical and Physical Sciences, University of Toronto, 3359 Mississauga Road North, Mississauga, Ontario L5L 1C6, Canada.
Chemical Society Reviews
|February 12, 2013
Summary
Synthetic agents targeting Src homology 2 (SH2) domains offer a promising therapeutic strategy. Disrupting SH2 domain function in over-activated proteins shows potential for treating diseases like cancer.
Area of Science:
- Molecular Biology
- Drug Discovery
- Biochemistry
Background:
- Src homology 2 (SH2) domains are critical protein modules mediating intracellular interactions by binding to tyrosyl-phosphorylated peptides.
- Over 110 human proteins contain SH2 domains, including key regulators like kinases and transcription factors.
- Dysregulation of SH2 domain-containing proteins is implicated in various diseases, notably cancer.
Purpose of the Study:
- To review the development of synthetic agents designed to inhibit SH2 domain functionality.
- To explore the clinical relevance and therapeutic potential of targeting specific SH2 domains.
Main Methods:
- Literature review focusing on synthetic agents and their mechanisms of action against SH2 domains.
- Analysis of the role of SH2 domains in disease pathogenesis.
- Evaluation of the feasibility of SH2 domain-targeted therapies.
Main Results:
- Significant progress has been made in developing synthetic agents that disrupt SH2 domain interactions.
- Targeting SH2 domains presents a viable strategy for inhibiting over-activated proteins in disease states.
- The development of SH2 domain inhibitors is a challenging yet feasible therapeutic approach.
Conclusions:
- Inhibiting SH2 domain function is a promising therapeutic avenue for diseases driven by protein dysregulation.
- Synthetic agents targeting SH2 domains represent a novel class of potential therapeutics.
- Further research into SH2 domain inhibition holds significant clinical relevance for cancer and other diseases.
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