ArticleProceedings of the National Academy of Sciences of the United States of America2016
Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 68 citations in OpenAlex.
- Intracellular Activation of Dual-Pharmacophore Artezomib Enhances Selective Cytotoxicity in Hematologic Malignancies.Journal of medicinal chemistry · 2026Article
- α-Aminoboronic Acid Moieties in Boro Dipeptides Modulate Proteasome Subunit Selectivity and Provide Access to Compounds with Potent Anticancer and Anti-Inflammatory Activity.Journal of medicinal chemistry · 2025Article
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Immunoproteasome Inhibition Impairs Differentiation but Not Survival of T Helper 17 Cells.Cells · 2025Article
- Recent Advances in the Development of Immunoproteasome Inhibitors as Anti-Cancer Agents: The Past 5 Years.Molecules (Basel, Switzerland) · 2025Review
- Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders.ACS chemical neuroscience · 2024Review
- The role of proteasomes in tumorigenesis.Genes & diseases · 2024Review
- Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.PLoS biology · 2024Article
- Immunoproteasome inhibition reduces donor specific antibody production and cardiac allograft vasculopathy in a mouse heart transplantation model.Frontiers in transplantation · 2024Article
- Discovery of Highly Selective Inhibitors of the Human Constitutive Proteasome β5c Chymotryptic Subunit.Journal of medicinal chemistry · 2023Article
- Review
- Targeting inflammation and immune activation to improve CTLA4-Ig-based modulation of transplant rejection.Frontiers in immunology · 2022Review
- Site-Specific Proteasome Inhibitors.Biomolecules · 2021Review
- Review
- A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential.Cells · 2021Review
- Noncytotoxic Inhibition of the Immunoproteasome Regulates Human Immune Cells In Vitro and Suppresses Cutaneous Inflammation in the Mouse.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Mitigated viral myocarditis in A/J mice by the immunoproteasome inhibitor ONX 0914 depends on inhibition of systemic inflammatory responses in CoxsackievirusB3 infection.Basic research in cardiology · 2021Article
- Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
Constitutive proteasomes (c-20S) are ubiquitously expressed cellular proteases that degrade polyubiquitinated proteins and regulate cell functions. An isoform of proteasome, the immunoproteasome (i-20S), is highly expressed in human T cells, dendritic cells (DCs), and B cells, suggesting that it could be a potential target for inflammatory diseases, including those involving autoimmunity and alloimmunity. Here, we describe DPLG3, a rationally designed, noncovalent inhibitor of the immunoproteasome chymotryptic subunit β5i that has thousands-fold selectivity over constitutive β5c. DPLG3 suppressed cytokine release from blood mononuclear cells and the activation of DCs and T cells, diminished accumulation of effector T cells, promoted expression of exhaustion and coinhibitory markers on T cells, and synergized with CTLA4-Ig to promote long-term acceptance of cardiac allografts across a major histocompatibility barrier. These findings demonstrate the potential value of using brief posttransplant immunoproteasome inhibition to entrain a long-term response favorable to allograft survival as part of an immunomodulatory regimen that is neither broadly immunosuppressive nor toxic.
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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.