ArticleNature chemical biology2017
Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed.
- Cobalt-Catalyzed Halogen-Retentive C-H Activation and Its Application in Medicinal Chemistry.JACS Au · 2026Article
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- CAND1 and CAND2 drive CUL4 substrate receptor exchange with largely comparable biochemical efficiency, unlike their relative effects on CUL1.Structure (London, England : 1993) · 2026Article
- From concept to application: Exploring the evolution and potential of DUBTAC technology.Acta pharmaceutica Sinica. B · 2026Review
- Old drugs, new weapons: current trends in repurposing therapies against antimicrobial resistance.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Psmd13, a proteasome regulatory subunit identified in miR-29a regulation during neuronal differentiation.PloS one · 2026Article
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- PSMD14 as a translational target in cancer and beyond: from deubiquitination mechanisms to drug resistance and precision therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy.Nature cell biology · 2025Article
- Molecular glues that inhibit deubiquitylase activity and inflammatory signaling.Nature structural & molecular biology · 2025Article
- 19S proteasome loss regulates mitotic spindle assembly through a ubiquitin-independent degradation mechanism.Cell reports · 2025Article
- NMR-Guided Studies to Establish the Binding Interaction between a Peptoid and Protein.Journal of the American Chemical Society · 2025Article
- p97/VCP is required for piecemeal autophagy of aggresomes.Nature communications · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- The adaptor protein AP-3β disassembles heat-induced stress granules via 19S regulatory particle in Arabidopsis.Nature communications · 2025Article
- PSMD14-mediated deubiquitination of CARM1 facilitates the proliferation and metastasis of hepatocellular carcinoma by inducing the transcriptional activation of FERMT1.Cell death & disease · 2025Article
- Molecular mechanisms of CAND2 in regulating SCF ubiquitin ligases.Nature communications · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Novel drug research and therapeutic strategies targeting tumor metastasis and cancer stem cells.Frontiers in pharmacology · 2025Review
38 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors.
Funding
Abstract
The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting of proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond to these compounds, and those who do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop new drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11. A derivative of 8TQ, capzimin, shows >5-fold selectivity for Rpn11 over the related JAMM proteases and >2 logs selectivity over several other metalloenzymes. Capzimin stabilized proteasome substrates, induced an unfolded protein response, and blocked proliferation of cancer cells, including those resistant to bortezomib. Proteomic analysis revealed that capzimin stabilized a subset of polyubiquitinated substrates. Identification of capzimin offers an alternative path to develop proteasome inhibitors for cancer therapy.
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