jhu395

JHU395 is an orally-bioavailable prodrug of a lipophilic glutamine antagonist (GA), 6-diazo-5-oxo-L-norleucine (DON). It demonstrates delivery of DON to malignant peripheral nerve sheath tumor (MPNST) both in vitro and in vivo, resulting in significant antitumor activity in MPNST. Additionally, JHU395 exhibits plasma stability.

Pro-905 is a phosphonate peptide with antitumor activity. It delivers the active nucleotide antimetabolite thioinosine monophosphate (TGMP) to tumors. Pro-905 effectively inhibits the binding of purine residue substrates to nucleic acids, thereby suppressing colony formation of human malignant peripheral nerve sheath tumor (MPNST) cells. It prevents purine residues from incorporating into nucleic acids, hindering cell growth. Additionally, Pro-905 inhibits the growth of MPNST and enhances the antitumor effect of JHU395.