ArticleBioorganic & medicinal chemistry2015
Strategies to make protein serine/threonine (PP1, calcineurin) and tyrosine phosphatases (PTP1B) druggable: achieving specificity by targeting substrate and regulatory protein interaction sites.
Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Intratracheal Delivery of a Phospholamban Decoy Peptide Attenuates Cardiac Damage Following Myocardial Infarction.International journal of molecular sciences · 2025Article
- PPP1R2 stimulates protein phosphatase-1 through stabilisation of dynamic subunit interactions.Nature communications · 2024Article
- A protein phosphatase 1 specificProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.ACS omega · 2024Article
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- Protein Tyrosine Phosphatase regulation by Reactive Oxygen Species.Advances in cancer research · 2024Review
- HIV-1 Transcription Inhibitor 1E7-03 Decreases Nucleophosmin Phosphorylation.Molecular & cellular proteomics : MCP · 2023Article
- Computational Methods in Cooperation with Experimental Approaches to Design Protein Tyrosine Phosphatase 1B Inhibitors in Type 2 Diabetes Drug Design: A Review of the Achievements of This Century.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Protein tyrosine phosphatases (PTPs) in diabetes: causes and therapeutic opportunities.Archives of pharmacal research · 2021Review
- Protein Tyrosine Phosphatases: A new paradigm in an old signaling system?Advances in cancer research · 2021Review
- Structural Optimization of 2,3-Dihydro-1H-cyclopenta[ACS infectious diseases · 2020Article
- Allosteric Impact of the Variable Insert Loop inBiochemistry · 2020Article
- SHOC2 complex-driven RAF dimerization selectively contributes to ERK pathway dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- SHOC2 phosphatase-dependent RAF dimerization mediates resistance to MEK inhibition in RAS-mutant cancers.Nature communications · 2019Article
- ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail.Nature communications · 2019Article
- Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus Inhibition.Frontiers in microbiology · 2019Article
- Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics.Biochimica et biophysica acta. Molecular cell research · 2019Review
- SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases.Molecules (Basel, Switzerland) · 2018Review
- Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides.Journal of peptide science : an official publication of the European Peptide Society · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The established dogma is that protein serine/threonine (PSPs) and tyrosine (PTPs) phosphatases are unattainable drug targets. This is because natural product inhibitors of PSP active sites are lethal, while the active sites of PTPs are exceptionally conserved and charged, making it nearly impossible to develop PTP inhibitors that are selective. However, due to a series of recent structural and functional studies, this view of phosphatases is about to undergo a radical change. Rather than target active sites, these studies have demonstrated that targeting PSP/PTP protein (substrate/regulatory) interaction sites, which are distal from the active sites, are highly viable and suitable drugs targets. This is especially true for calcineurin (CN), in which the blockbuster immunosuppressant drugs FK506 and cyclosporin A were recently demonstrated to bind and block one of the key CN substrate interaction sites, the LxVP site. Additional studies show that this approach-targeting substrate and/or regulatory protein interaction sites-also holds incredible promise for protein phosphatase 1 (PP1)-related diseases. Finally, domains outside PTP catalytic domains have also recently been demonstrated to directly alter PTP activity. Collectively, these novel insights offer new, transformative perspectives for the therapeutic targeting of PSPs by interfering with the binding of PIPs or substrates and PTPs by targeting allosteric sites outside their catalytic domains.
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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.