ArticleJournal of the American Chemical Society2016
Selective Phosphorylation Inhibitor of Delta Protein Kinase C-Pyruvate Dehydrogenase Kinase Protein-Protein Interactions: Application for Myocardial Injury in Vivo.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Applications of Graphene Field Effect Biosensors for Biological Sensing.Advances in biochemical engineering/biotechnology · 2024Review
- An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- An Update on Protein Kinases as Therapeutic Targets-Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein-Protein Interactions.International journal of molecular sciences · 2023Review
- Demonstration of the Early Cardiac Bioavailability of a Non-Specific Cell-Targeted Peptide Using Radionuclide-Based Imaging In Vivo.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Selective inhibitors targeting Fis1/Mid51 protein-protein interactions protect against hypoxia-induced damage in cardiomyocytes.Frontiers in pharmacology · 2023Article
- A novel mRNA decay inhibitor abolishes pathophysiological cellular transition.Cell death discovery · 2022Article
- De Novo Development of Mitochondria-Targeted Molecular Probes Targeting Pink1.International journal of molecular sciences · 2022Article
- Disrupting the MAD2L2-Rev1 Complex Enhances Cell Death upon DNA Damage.Molecules (Basel, Switzerland) · 2022Article
- Myocardial Proteomics Based on Smart Fog Computing and Its Application in Sports.Computational intelligence and neuroscience · 2022Article
- A Genetic Toggle for Chemical Control of Individual Plk1 Substrates.Cell chemical biology · 2020Article
- Digital Biosensing by Foundry-Fabricated Graphene Sensors.Scientific reports · 2019Article
- A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats.Nature communications · 2019Article
- Target-based drug discovery through inversion of quantitative structure-drug-property relationships and molecular simulation: CA IX-sulphonamide complexes.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death.Cell research · 2018Article
- Enzyme sequestration by the substrate: An analysis in the deterministic and stochastic domains.PLoS computational biology · 2018Article
- Peptides and peptidomimetics as regulators of protein-protein interactions.Current opinion in structural biology · 2017Review
- Engineered Substrate-Specific Delta PKC Antagonists to Enhance Cardiac Therapeutics.Angewandte Chemie (International ed. in English) · 2016Article
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Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinases regulate numerous cellular processes, including cell growth, metabolism, and cell death. Because the primary sequence and the three-dimensional structure of many kinases are highly similar, the development of selective inhibitors for only one kinase is challenging. Furthermore, many protein kinases are pleiotropic, mediating diverse and sometimes even opposing functions by phosphorylating multiple protein substrates. Here, we set out to develop an inhibitor of a selective protein kinase phosphorylation of only one of its substrates. Focusing on the pleiotropic delta protein kinase C (δPKC), we used a rational approach to identify a distal docking site on δPKC for its substrate, pyruvate dehydrogenase kinase (PDK). We reasoned that an inhibitor of PDK's docking should selectively inhibit the phosphorylation of only PDK without affecting phosphorylation of the other δPKC substrates. Our approach identified a selective inhibitor of PDK docking to δPKC with an in vitro Kd of ∼50 nM and reducing cardiac injury IC50 of ∼5 nM. This inhibitor, which did not affect the phosphorylation of other δPKC substrates even at 1 μM, demonstrated that PDK phosphorylation alone is critical for δPKC-mediated injury by heart attack. The approach we describe is likely applicable for the identification of other substrate-specific kinase inhibitors.
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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.