JHU083

JHU083 is an experimental, orally administered small molecule prodrug designed to inhibit glutamine metabolism in tumors. It is a tumor-targeted derivative of 6-diazo-5-oxo-L-norleucine (DON), a broad-spectrum glutamine antagonist. The prodrug remains inactive in circulation and is selectively converted into its active form within the tumor microenvironment, thereby minimizing systemic toxicity. Mechanistically, JHU083 blocks glutaminase and other glutamine-utilizing enzymes, disrupting cancer cell metabolism and reprogramming the tumor microenvironment. This leads to direct impairment of glutamine-dependent cancer cells and reprograms immunosuppressive tumor-associated macrophages (TAMs) into inflammatory, immune-stimulating phenotypes with increased phagocytic activity. Additionally, it enhances anti-tumor T-cell responses by promoting immune memory formation and can synergize with immunotherapies such as checkpoint inhibitors or adoptive cell therapies like CAR-T cells[1][3][5][6][7][8].

Other names

6-diazo-5-oxo-L-norleucine prodrugDON prodrug