Chemistry:JHU-083
From HandWiki
Short description: Experimental Drug
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| Formula | C14H24N4O4 |
| Molar mass | 312.370 g·mol−1 |
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JHU-083 is an experimental drug which acts as a glutaminase inhibitor. It is a prodrug which is cleaved in vivo to the active form 6-diazo-5-oxo-L-norleucine. It has been researched for the treatment of various neurological conditions such as depression, Alzheimer's disease, and cerebral malaria,[1][2][3] as well as multiple sclerosis,[4] atherosclerosis,[5] hepatitis,[6] and some forms of cancer in which it was found to target senescent cells.[7][8][9][10]
References
- ↑ "JHU-083 selectively blocks glutaminase activity in brain CD11b+ cells and prevents depression-associated behaviors induced by chronic social defeat stress". Neuropsychopharmacology 44 (4): 683–694. March 2019. doi:10.1038/s41386-018-0177-7. PMID 30127344.
- ↑ "Glutamine Antagonist JHU-083 Normalizes Aberrant Hippocampal Glutaminase Activity and Improves Cognition in APOE4 Mice". Journal of Alzheimer's Disease 77 (1): 437–447. 2020. doi:10.3233/JAD-190588. PMID 32675407.
- ↑ "MRI demonstrates glutamine antagonist-mediated reversal of cerebral malaria pathology in mice". Proceedings of the National Academy of Sciences of the United States of America 115 (51): E12024–E12033. December 2018. doi:10.1073/pnas.1812909115. PMID 30514812. Bibcode: 2018PNAS..11512024R.
- ↑ "Glutamine antagonism attenuates physical and cognitive deficits in a model of MS". Neurology 6 (6): e609. November 2019. doi:10.1212/NXI.0000000000000609. PMID 31467038.
- ↑ "Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation". International Journal of Molecular Sciences 22 (11): 5602. May 2021. doi:10.3390/ijms22115602. PMID 34070527.
- ↑ "Glutaminase 1 blockade alleviates nonalcoholic steatohepatitis via promoting proline metabolism". Biochemical and Biophysical Research Communications 634: 1–9. December 2022. doi:10.1016/j.bbrc.2022.10.007. PMID 36223657.
- ↑ "Orally bioavailable glutamine antagonist prodrug JHU-083 penetrates mouse brain and suppresses the growth of MYC-driven medulloblastoma". Translational Oncology 12 (10): 1314–1322. October 2019. doi:10.1016/j.tranon.2019.05.013. PMID 31340195.
- ↑ "The glutamine antagonist prodrug JHU-083 slows malignant glioma growth and disrupts mTOR signaling". Neuro-Oncology Advances 3 (1): vdaa149. 2021. doi:10.1093/noajnl/vdaa149. PMID 33681764.
- ↑ "Targeting Glutamine Metabolism to Enhance Immunoprevention of EGFR-Driven Lung Cancer". Advanced Science 9 (26): e2105885. September 2022. doi:10.1002/advs.202105885. PMID 35861366.
- ↑ "In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma". Science Advances 8 (50): eabp8293. December 2022. doi:10.1126/sciadv.abp8293. PMID 36525494. Bibcode: 2022SciA....8P8293K.
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