ARTICLE | Distillery Therapeutics


August 16, 2017 6:00 PM UTC

Mouse and pig studies identified a GLS inhibitor prodrug that could help treat HIV-associated neurocognitive disorders. In a mouse model of HIV-associated neurocognitive dysfunction, the GLS inhibitor 6-diazo-5-oxo-L-norleucine (DON) increased spatial learning and memory compared with vehicle. Chemical synthesis and testing of pivaloyloxymethylester-functionalized DON prodrugs in pig-based assays of CNS penetration yielded two compounds that had a higher CSF-to-plasma ratio than the parent compound. Next steps by Dracen Pharmaceuticals Inc. include selecting a compound from the series for IND-enabling studies.

New Medical Enzymes AG and Nektar Therapeutics have GlutaDON, DON combined with the enzyme PEGylated glutaminase (PEG-PGA), in Phase II testing to treat non-small cell lung cancer (NSCLC), solid tumors, colorectal cancer, gastric cancer and renal cancer. ...