ArticleJournal of the American Chemical Society2012
A highly selective and potent PTP-MEG2 inhibitor with therapeutic potential for type 2 diabetes.
Article in Journal of the American Chemical Society, 2012. 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, 56 citations in OpenAlex.
- Recent advances of dual PROTACs for potential therapeutic applications.Molecular diversity · 2026Review
- WatCon: A Python Tool for Analysis of Conserved Water Networks Across Protein Families.JACS Au · 2025Article
- Discovery and Evaluation of Active Site-Directed, Potent, and Selective Sulfophenyl Acetic Amide-Based Inhibitors for the Laforin Phosphatase.Journal of medicinal chemistry · 2025Article
- Review
- Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases.Journal of medicinal chemistry · 2024Article
- Burdock miR8175 in diet improves insulin resistance induced by obesity in mice through food absorption.iScience · 2024Article
- Exploring the Anti-Diabetic Potential of Quercetagitrin through Dual Inhibition of PTPN6 and PTPN9.Nutrients · 2024Article
- Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy.Angewandte Chemie (International ed. in English) · 2023Article
- Article
- Pharmacological Activities of Ginkgolic Acids in Relation to Autophagy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Structure-Activity Relationship of Synthetic Ginkgolic Acid Analogs for Treating Type 2 Diabetes by PTPN9 Inhibition.International journal of molecular sciences · 2022Article
- PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.EMBO reports · 2021Article
- Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance.Molecules (Basel, Switzerland) · 2021Article
- Recent advances in synthetic and medicinal chemistry of phosphotyrosine and phosphonate-based phosphotyrosine analogues.RSC medicinal chemistry · 2020Review
- Targeting Protein-Protein Interactions of Tyrosine Phosphatases with Microarrayed Fragment Libraries Displayed on Phosphopeptide Substrate Scaffolds.ACS combinatorial science · 2019Article
- High Expression of PTPN3 Predicts Progression and Unfavorable Prognosis of Glioblastoma.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126.Oncology letters · 2017Article
- Synthesis, bioactivity, 3D-QSAR studies of novel dibenzofuran derivatives as PTP-MEG2 inhibitors.Oncotarget · 2017Article
- Drugging the Undruggable: Therapeutic Potential of Targeting Protein Tyrosine Phosphatases.Accounts of chemical research · 2017Article
- Modulation of VEGF receptor 2 signaling by protein phosphatases.Pharmacological research · 2017Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Protein tyrosine phosphatases (PTPs) constitute a large family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. A detailed understanding of PTP functions in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific, cell-permeable small-molecule agents. We present a stepwise focused library approach that transforms a weak and general non-hydrolyzable pTyr mimetic (F(2)Pmp, phosphonodifluoromethyl phenylalanine) into a highly potent and selective inhibitor of PTP-MEG2, an antagonist of hepatic insulin signaling. The crystal structures of the PTP-MEG2-inhibitor complexes provide direct evidence that potent and selective PTP inhibitors can be obtained by introducing molecular diversity into the F(2)Pmp scaffold to engage both the active site and unique nearby peripheral binding pockets. Importantly, the PTP-MEG2 inhibitor possesses highly efficacious cellular activity and is capable of augmenting insulin signaling and improving insulin sensitivity and glucose homeostasis in diet-induced obese mice. The results indicate that F(2)Pmp can be converted into highly potent and selective PTP inhibitory agents with excellent in vivo efficacy. Given the general nature of the approach, this strategy should be applicable to other members of the PTP superfamily.
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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.