JHU395 is orally-bioavailable glutamine antagonist prodrug, shows antitumor activity in malignant peripheral nerve sheath tumor (MPNST, sNF96.2 cell growth IC50=4.6 uM).
JHU395 exhibits increased metabolic stability in swine and human plasma, favorable conversion in brain homogenate, and substantially improved CNS delivery in vivo in swine, compare with 6-diazo-5-oxo-L-norleucine (DON).
JHU395 attenuates glutamate synthesis in HIV-infected microglia/macrophages, offering therapeutic potential for HIV-associated neurocognitive disorders (HAND).
JHU395 also decreased growth and increased apoptosis in multiple human high-MYC medulloblastoma cell lines at lower concentrations than DON.
