ArticleTranslational oncology2019
Orally bioavailable glutamine antagonist prodrug JHU-083 penetrates mouse brain and suppresses the growth of MYC-driven medulloblastoma.
Article in Translational oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 72 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- A Boronic Acid-Based Glutamine Analog Forms a Covalent Adduct with Kidney-Type Glutaminase and Suppresses Triple-Negative Breast Cancer Cell Proliferation.Biomedicines · 2026Article
- Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- Immune checkpoint inhibitors in medulloblastoma: current updates in preclinical and clinical developments.Frontiers in oncology · 2026Review
- Host systemic metabolism and cancer metabolic vulnerabilities: mechanisms and therapeutic opportunities.Frontiers in oncology · 2026Review
- Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Inhibition of Glutamine Metabolism Attenuates Tumor Progression Through Remodeling of the Macrophage Immune Microenvironment.Advanced biology · 2025Article
- Beyond the tumor: Enhancing pancreatic cancer therapy through glutamine metabolism and innovative drug delivery.Journal of cell communication and signaling · 2025Review
- Metabolism, a Blossoming Target for Small-Molecule Anticancer Drugs.Molecules (Basel, Switzerland) · 2025Review
- Glutaminase inhibition ameliorates cancer-associated fibroblast lipid support of pancreatic cancer cell growth.Cancer & metabolism · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- A hormetic response model for glutamine stress in cancer.Trends in cancer · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma.BMC medicine · 2024Review
- Glutaminase inhibition as potential cancer therapeutics: current status and future applications.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- Targeting the glutamine-arginine-proline metabolism axis in cancer.Journal of enzyme inhibition and medicinal chemistry · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
A subset of poor-prognosis medulloblastoma has genomic amplification of MYC. MYC regulates glutamine metabolism in multiple cellular contexts. We modified the glutamine analog 6-diazo-5-oxo-l-norleucine (DON) to mask its carboxylate and amine functionalities, creating a prodrug termed JHU-083 with increased oral bioavailability. We hypothesized that this prodrug would kill MYC-expressing medulloblastoma. JHU-083 treatment caused decreased growth and increased apoptosis in human MYC-expressing medulloblastoma cell lines. We generated a mouse MYC-driven medulloblastoma model by transforming C57BL/6 mouse cerebellar stem and progenitor cells. When implanted into the brains of C57BL/6 mice, these cells formed large cell/anaplastic tumors that resembled aggressive medulloblastoma. A cell line derived from this model was sensitive to JHU-083 in vitro. Oral administration of JHU-038 led to the accumulation of micromolar concentrations of DON in the mouse brain. JHU-083 treatment significantly increased the survival of immune-competent animals bearing orthotopic tumors formed by the mouse cerebellar stem cell model as well as immune-deficient animals bearing orthotopic tumors formed by a human MYC-amplified medulloblastoma cell line. These data provide pre-clinical justification for the ongoing development and testing of orally bioavailable DON prodrugs for use in medulloblastoma patients.
Identifiers
What OpenQuestion holds
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.