D-JHU29

D-JHU29 is a dendrimer-based prodrug of the glutaminase inhibitor JHU29 (itself a prodrug of the glutamine antagonist 6-diazo-5-oxo-L-norleucine, or DON). Developed by researchers at Johns Hopkins University, D-JHU29 is designed to selectively target microglial cells, thereby inhibiting microglial glutaminase (GLS1) activity while minimizing systemic exposure and associated gastrointestinal toxicity. Glutaminase is often upregulated in activated microglia during neuroinflammatory states, contributing to the pathophysiology of various psychiatric and neurological conditions. In preclinical models of chronic social defeat stress (CSDS), D-JHU29 has demonstrated the ability to reduce microglial GLS1 activity in the hippocampus and prefrontal cortex, leading to improvements in behavioral deficits such as impaired sociability and exploratory behavior. This targeted approach represents a novel therapeutic strategy for major depressive disorder (MDD) and other stress-induced psychiatric conditions.