ArticleNeuro-oncology2016
Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier.
Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03727841 (Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma), which is not on this map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial.Neuro-oncology · 2024Trial
- Preclinical evaluation of ixazomib for high-risk pediatric brain tumors.bioRxiv : the preprint server for biology · 2026Article
- Nanoparticle-Based delivery of proteasome inhibitors for glioblastoma Therapy: Strategies to overcome Blood-Brain barrier and therapeutic resistance.Biochemical pharmacology · 2026Review
- Generation and MHC class II loading of an endogenous influenza epitope revealed by a T cell receptor-like antibody.bioRxiv : the preprint server for biology · 2026Article
- Automated and personalized glioblastoma tumor organoid drug screening platform exposes sensitivity to proteasome and HDAC inhibitors.NPJ precision oncology · 2026Article
- Central nervous system multiple myeloma: An update for 2026.Annals of hematology · 2026Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- From Deep-Sea Natural Product to Optimized Therapeutics: Computational Design of Marizomib Analogs.International journal of molecular sciences · 2025Article
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- Development of Macrocyclic Peptide-Based Proteasome Inhibitors with Enhanced Blood-Brain Barrier Penetration for Treating Brain Neoplasms.Journal of medicinal chemistry · 2025Article
- Exploring theAntimicrobial agents and chemotherapy · 2025Article
- MG132 induces cell type‑specific anticancer effects in uterine leiomyosarcoma cell lines.Molecular medicine reports · 2025Article
- Dual targeting of the mitochondrial Lon peptidase 1 and the chymotrypsin-like proteasome activity as a potential therapeutic strategy in malignant astrocytoma models.Pharmacological research · 2025Article
- Structural Insights into Salinosporamide a Mediated Inhibition of the Human 20S Proteasome.Molecules (Basel, Switzerland) · 2025Article
- Structural insights into Salinosporamide A mediated inhibition of the human 20S proteasome.bioRxiv : the preprint server for biology · 2025Article
- Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors.Nature communications · 2024Article
- Proteasome inhibition for glioblastoma: Lessons learned and new opportunities.Neuro-oncology · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe proteasome plays a vital role in the physiology of glioblastoma (GBM), and proteasome inhibition can be used as a strategy for treating GBM. Marizomib is a second-generation, irreversible proteasome inhibitor with a more lipophilic structure that suggests the potential for penetrating the blood-brain barrier. While bortezomib and carfilzomib, the 2 proteasome inhibitors approved for treatment of multiple myeloma, have little activity against malignant gliomas in vivo, marizomib could be a novel therapeutic strategy for primary brain tumors.
methodsThe in-vitro antitumor activity of marizomib was studied in glioma cell lines U-251 and D-54. The ability of marizomib to cross the blood-brain barrier and regulate proteasome activities was evaluated in cynomolgus monkeys and rats. The antitumor effect of marizomib in vivo was tested in an orthotopic xenograft model of human GBM.
resultsMarizomib inhibited the proteasome activity, proliferation, and invasion of glioma cells. Meanwhile, free radical production and apoptosis induced by marizomib could be blocked by antioxidant N-acetyl cysteine. In animal studies, marizomib distributed into the brain at 30% of blood levels in rats and significantly inhibited (>30%) baseline chymotrypsin-like proteasome activity in brain tissue of monkeys. Encouragingly, the immunocompromised mice, intracranially implanted with glioma xenografts, survived significantly longer than the control animals (P < .05) when treated with marizomib.
conclusionsThese preclinical studies demonstrated that marizomib can cross the blood-brain barrier and inhibit proteasome activity in rodent and nonhuman primate brain and elicit a significant antitumor effect in a rodent intracranial model of malignant glioma.
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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.