ArticleNature communications2017
Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Structure-Activity Relationship Study of Antimalarial Asparagine-Derived Proteasome Inhibitors.ACS omega · 2026Article
- Intracellular Activation of Dual-Pharmacophore Artezomib Enhances Selective Cytotoxicity in Hematologic Malignancies.Journal of medicinal chemistry · 2026Article
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- Decoding efficacy and resistance space at a drug binding site.Nature communications · 2026Article
- Novel de novo dominantJournal of human immunity · 2026Article
- 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
- Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.PLoS biology · 2024Article
- Virtual Screening Strategy and In Vitro Tests to Identify New Inhibitors of the Immunoproteasome.International journal of molecular sciences · 2023Article
- PfCRT mutations conferring piperaquine resistance in falciparum malaria shape the kinetics of quinoline drug binding and transport.PLoS pathogens · 2023Article
- Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin-proteasome system to kill malaria parasites while overcoming drug resistance.Cell chemical biology · 2023Article
- Identification of a new class of proteasome inhibitors based on a naphthyl-azotricyclic-urea-phenyl scaffold.RSC medicinal chemistry · 2023Article
- Discovery of Highly Selective Inhibitors of the Human Constitutive Proteasome β5c Chymotryptic Subunit.Journal of medicinal chemistry · 2023Article
- Activation of immune cell proteasomes in peripheral blood of smokers and COPD patients: implications for therapy.The European respiratory journal · 2022Article
- Site-Specific Proteasome Inhibitors.Biomolecules · 2021Review
- Microbial proteasomes as drug targets.PLoS pathogens · 2021Review
- M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models.Molecular cancer therapeutics · 2021Article
- A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential.Cells · 2021Review
- Current approach and novel perspectives in nasopharyngeal carcinoma: the role of targeting proteasome dysregulation as a molecular landmark in nasopharyngeal cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Development of a Highly Selective Plasmodium falciparum Proteasome Inhibitor with Anti-malaria Activity in Humanized Mice.Angewandte Chemie (International ed. in English) · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Proteasome inhibitors benefit patients with multiple myeloma and B cell-dependent autoimmune disorders but exert toxicity from inhibition of proteasomes in other cells. Toxicity should be minimized by reversible inhibition of the immunoproteasome β5i subunit while sparing the constitutive β5c subunit. Here we report β5i-selective inhibition by asparagine-ethylenediamine (AsnEDA)-based compounds and present the high-resolution cryo-EM structural analysis of the human immunoproteasome. Despite inhibiting noncompetitively, an AsnEDA inhibitor binds the active site. Hydrophobic interactions are accompanied by hydrogen bonding with β5i and β6 subunits. The inhibitors are far more cytotoxic for myeloma and lymphoma cell lines than for hepatocarcinoma or non-activated lymphocytes. They block human B-cell proliferation and promote apoptotic cell death selectively in antibody-secreting B cells, and to a lesser extent in activated human T cells. Reversible, β5i-selective inhibitors may be useful for treatment of diseases involving activated or neoplastic B cells or activated T cells.
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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.