ArticleMolecular cancer therapeutics2013
Targeting protein tyrosine phosphatase SHP2 for the treatment of PTPN11-associated malignancies.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Targeting RNA-Binding Oncofetal Protein IGF2BP3: Discovery of Potent and Selective Inhibitors.Journal of medicinal chemistry · 2026Article
- Case Report: Genomic characterization of a rare skull-base plasmacytoma.Frontiers in oncology · 2025Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- Targeting SHP2 with an Active Site Inhibitor Blocks Signaling and Breast Cancer Cell Phenotypes.ACS bio & med chem Au · 2023Article
- RETRACTED: Protein Tyrosine Phosphatase Non-Receptor 11 (International journal of molecular sciences · 2023Article
- Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022Review
- Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.International journal of molecular sciences · 2022Article
- Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies.Acta pharmaceutica Sinica. B · 2021Review
- Novel Small-Molecule Inhibitor for the Oncogenic Tyrosine Phosphatase SHP2 with Anti-Breast Cancer Cell Effects.ACS omega · 2020Article
- Clinical Utility of Next-Generation Sequencing in Acute Myeloid Leukemia.Molecular diagnosis & therapy · 2020Review
- Profiling Protein Tyrosine Phosphatase Specificity with Self-Assembled Monolayers for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry and Peptide Arrays.ACS combinatorial science · 2019Article
- Review
- HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis.Nature communications · 2018Article
- Gain-of-function mutations in the gene encoding the tyrosine phosphatase SHP2 induce hydrocephalus in a catalytically dependent manner.Science signaling · 2018Article
- Protein tyrosine phosphatases in cardiac physiology and pathophysiology.Heart failure reviews · 2018Review
- Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers.Cancers · 2018Article
- Combining SAMDI Mass Spectrometry and Peptide Arrays to Profile Phosphatase Activities.Methods in enzymology · 2018Article
- Discovery of a Novel Inhibitor of the Protein Tyrosine Phosphatase Shp2.Scientific reports · 2015Article
- Shp2 and Pten have antagonistic roles in myeloproliferation but cooperate to promote erythropoiesis in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Functions of Shp2 in cancer.Journal of cellular and molecular medicine · 2015Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Activating mutations in PTPN11 (encoding SHP2), a protein tyrosine phosphatase (PTP) that plays an overall positive role in growth factor and cytokine signaling, are directly associated with the pathogenesis of Noonan syndrome and childhood leukemias. Identification of SHP2-selective inhibitors could lead to the development of new drugs that ultimately serve as treatments for PTPN11-associated diseases. As the catalytic core of SHP2 shares extremely high homology to those of SHP1 and other PTPs that play negative roles in cell signaling, to identify selective inhibitors of SHP2 using computer-aided drug design, we targeted a protein surface pocket that is adjacent to the catalytic site, is predicted to be important for binding to phosphopeptide substrates, and has structural features unique to SHP2. From computationally selected candidate compounds, #220-324 effectively inhibited SHP2 activity with an IC50 of 14 μmol/L. Fluorescence titration experiments confirmed its direct binding to SHP2. This active compound was further verified for its ability to inhibit SHP2-mediated cell signaling and cellular function with minimal off-target effects. Furthermore, mouse myeloid progenitors with the activating mutation (E76K) in PTPN11 and patient leukemic cells with the same mutation were more sensitive to this inhibitor than wild-type cells. This study provides evidence that SHP2 is a "druggable" target for the treatment of PTPN11-associated diseases. As the small-molecule SHP2 inhibitor identified has a simple chemical structure, it represents an ideal lead compound for the development of novel anti-SHP2 drugs. Mol Cancer Ther; 12(9); 1738-48. ©2013 AACR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.