Biological Activity
RRx-001 is a novel epigenetic modulator with potential radiosensitizing activity. In human tumor cells, it inhibits glucose 6-phosphate dehydrogenase (G6PD), binds to hemoglobin and drives RBC-mediated redox reactions under hypoxia.It can trigger apoptosis and has antitumor activity.
in vitro
RRx-001 exerts its antiproliferative effect by interfering with glucose 6 phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway. RRx-001 induces p53 and PARP-1 through ROS/RNS generation. It exerts its anticancer activity by interfering and disrupting 3 crucial metabolic demands in rapidly proliferating cells: bioenergetics, macromolecular biosynthesis and manipulation of cellular cytoplasmic redox homeostasis.RRx-001 also mediates the nuclear translocation of Nrf2 and the expression of its downstream HO-1 and NQO1 in tumor cells.
in vivo
RRx-001 has a short-term blood flow redistribution effect in tumors enriched in pericytes and α-SMA vessels.It was well tolerated without dose-limiting toxic side effects. In mice, it not only promoted nuclear transport of Nrf2, but also upregulated the expression of endogenous Nrf2 in SCC VII tumors.
target
| Target | Value |
G6PD
() |
| Nrf2-ARE |
