Diazooxohexanoate-based prodrug of a GLS inhibitor for lymphoma

INDICATION: Lymphoma

Cell culture studies identified a diazooxohexanoate-based prodrug of a GLS inhibitor that could help treat lymphoma. Chemical synthesis and screening of ester prodrugs of the GLS inhibitor 6-diazo-5-oxo-L-norleucine (DON) in a human lymphoma cell line suspended in human plasma yielded a diazooxohexanoate-based prodrug that increased the tumor cell-to-plasma ratio of DON by 55-fold over the parent compound. In the cell line, the prodrug decreased proliferation compared with DON (EC₅₀ values of 10 and 5 μM, respectively). Next steps could include testing the prodrug in mouse models of lymphoma...