What Is JHU-083? Definition and What Research Reports

Definition

JHU-083 is a laboratory compound code for an orally bioavailable, small-molecule prodrug of a glutamine antagonist — a molecule designed to be inactive in circulation and then converted to an active glutamine-analogue drug within target tissues, where it blocks glutamine-utilising enzymes such as glutaminase. It has no brand name and no approved medical product associated with it; every reference in the verified literature below describes work in cultured cells and animal models. Because glutamine metabolism fuels both rapidly dividing tumour cells and activated immune cells, the compound has been examined in two broad research areas: cancer models and neuro-immune/behavioural models. This page is for educational purposes only and is not medical advice; consult a licensed physician about any health decision or medical question.

What Class of Molecule Is JHU-083?

JHU-083 is a small molecule, not a peptide. That distinction matters for anyone encountering the term in a peptide glossary. Peptides are short chains of amino acids linked by peptide bonds; JHU-083 is a chemically masked glutamine analogue. The masking groups are what make it a prodrug: they are intended to limit exposure of healthy tissue and to allow the active glutamine antagonist to be released where the relevant enzymes are concentrated.

Mechanistically, the published titles describe it in two overlapping ways. Some papers call it a "glutamine antagonist prodrug," reflecting that the released species competes with glutamine at multiple glutamine-dependent enzymes (PMID 33681764). Others describe it as a glutaminase inhibitor, reflecting the specific enzyme that converts glutamine to glutamate (PMID 40812515). Both descriptions point to the same idea: interrupting the supply of glutamine-derived carbon and nitrogen to cells that depend on it.

Why glutamine is the target

Glutamine is the most abundant free amino acid in plasma and a substrate for energy production, nucleotide synthesis and — in the brain — neurotransmitter cycling. Cells with high metabolic demand, including many tumour cells and activated myeloid immune cells, upregulate glutamine uptake and glutaminase activity. Research on JHU-083 has therefore asked whether pharmacologically constraining that pathway changes tumour growth, immune-cell behaviour, or neurochemistry.

Where the Term Comes From

"JHU-083" is an academic compound code rather than a commercial or international nonproprietary name. Codes of this form are assigned inside a drug-discovery programme to track analogues in a chemical series, and they persist into the peer-reviewed literature when a compound advances into animal studies. Because there is no approved product, the code is the only name used across the publications cited here — which is why the term surfaces in glossaries and research-compound indexes rather than in prescribing references.

How the Term Is Used in Research Writing

In practice, authors use "JHU-083" in three recurring contexts:

• As an oncology tool compound — to test whether blocking glutamine metabolism slows tumour growth or alters signalling pathways in cancer models.
• As a neuro-immune probe — to test whether inhibiting glutaminase in brain immune cells changes behaviour in stress models.
• As a brain-penetrant prodrug example — cited when discussing prodrug strategies intended to cross the blood–brain barrier and be unmasked in the central nervous system (PMID 31340195).

It is not used in the literature as a peptide therapeutic, a hormone secretagogue, or a metabolic supplement, and none of the verified papers describe human use.

What the Published Literature Reports

Cancer models

In a 2021 report in Neuro-Oncology Advances, researchers described the glutamine antagonist prodrug JHU-083 as slowing malignant glioma growth and disrupting mTOR signalling, linking glutamine blockade to a nutrient-sensing pathway that tumours rely on (PMID 33681764). Earlier, a 2019 study in Translational Oncology reported that the orally bioavailable prodrug penetrated mouse brain and suppressed the growth of MYC-driven medulloblastoma, a paediatric brain tumour subtype (PMID 31340195). Taken together, the study titles in this set frame brain penetration and oral bioavailability as the practical features that made central-nervous-system tumour models feasible.

Stress, depression-associated behaviour and brain immune cells

A 2019 Neuropsychopharmacology paper reported that JHU-083 selectively blocked glutaminase activity in brain CD11b⁺ cells — a marker used for microglia and related myeloid cells — and prevented depression-associated behaviours induced by chronic social defeat stress in mice (PMID 30127344). A formal correction to that article was subsequently published in the same journal (PMID 30862949); readers tracing the primary data should consult both records, since corrections can affect figures, panels or attribution.

Cognition in genetic-risk and PTSD models

A 2020 paper in the Journal of Alzheimer's Disease reported that the glutamine antagonist normalised aberrant hippocampal glutaminase activity and improved cognition in APOE4 mice, a model carrying the human APOE ε4 genetic risk variant (PMID 32675407). More recently, a 2025 study in Neuropharmacology reported that the glutaminase inhibitor JHU-083 mitigated cognitive dysfunction in a mouse model of post-traumatic stress disorder (PMID 40812515). Both are animal-model findings and do not establish an effect in people.

Study Snapshot

Safety and Tolerability: What Studies Report

The verified publications in this entry were designed around efficacy and mechanism endpoints in animals — tumour growth, enzyme activity, behaviour and cognition — rather than as human safety studies, and none of them reported adverse-event data in people (PMID 33681764, PMID 30127344, PMID 32675407). The prodrug design itself is described in the literature as a strategy intended to improve tissue targeting of a glutamine antagonist, including delivery to brain (PMID 31340195). Because glutamine metabolism is used by normal proliferating tissues as well as tumour and activated immune cells, tolerability is an open question that animal efficacy papers alone cannot answer.

Limitations and Context

• Preclinical only. Every finding summarised above came from cell or rodent work; species differences in metabolism and in prodrug activation are substantial.
• Model-specific endpoints. "Improved cognition" in APOE4 mice refers to defined behavioural tasks in that study (PMID 32675407), not to a clinical outcome.
• A published correction exists for one of the foundational behavioural papers (PMID 30862949), a reminder to read primary sources rather than summaries.
• Not a peptide. Grouping JHU-083 with peptides is a cataloguing convenience, not a chemical classification.

Related Terms

• Glutamine antagonist — a compound that competes with glutamine at glutamine-using enzymes.
• Glutaminase — the enzyme converting glutamine to glutamate, named as the target in the 2025 PTSD-model report (PMID 40812515).
• Prodrug — an inactive precursor converted to an active drug in the body.
• CD11b⁺ cells — myeloid immune cells, including microglia, examined in the chronic social defeat stress work (PMID 30127344).

References

• The glutamine antagonist prodrug JHU-083 slows malignant glioma growth and disrupts mTOR signaling (Neuro-Oncology Advances, 2021)
• Glutamine Antagonist JHU-083 Normalizes Aberrant Hippocampal Glutaminase Activity and Improves Cognition in APOE4 Mice (Journal of Alzheimer's Disease, 2020)
• The glutaminase inhibitor JHU-083 mitigates cognitive dysfunction in a mouse model of post-traumatic stress disorder (Neuropharmacology, 2025)
• Orally bioavailable glutamine antagonist prodrug JHU-083 penetrates mouse brain and suppresses the growth of MYC-driven medulloblastoma (Translational Oncology, 2019)
• JHU-083 selectively blocks glutaminase activity in brain CD11b(+) cells and prevents depression-associated behaviors induced by chronic social defeat stress (Neuropsychopharmacology, 2019)
• Correction: JHU-083 selectively blocks glutaminase activity in brain CD11b(+) cells and prevents depression-associated behaviors induced by chronic social defeat stress (Neuropsychopharmacology, 2019)