JHU395 is a novel orally bioavailable GA (glutamine antagonists) prodrug designed to circulate inert in plasma, but permeate and release active GA within target tissues. JHU395 delivers active GA to malignant peripheral nerve sheath tumor (MPNST), and significantly inhibits tumor growth without observed toxicity.
JHU395 inhibits growth of multiple biosynthetic processes by tumors (MPNST) cells, while growth of immortalized Schwann cells is minimally affected. JHU395 induces less PARP cleavage as a marker of apoptosis in human MPNST cells. JHU395 is a plasma stable lipophilic GA prodrug which delivers DON to MPNST in an in vitro plasma to tumor cell partitioning assay measurement.[1]
In vivo, orally administered JHU395 delivers active GA to tumors with over twofold higher tumor-to-plasma exposure, and significantly inhibits tumor growth in a murine flank MPNST model without observed toxicity.[1]
[1] Lemberg KM, et al. Mol Cancer Ther. 2020 Feb;19(2):397-408.