RUN-47 is a small-molecule activator of NRF1 with EC50 of 6.43 uM in 3xPSMA4-ARE-LUC reporter assays, specifically activates NRF1 pathway.
RUN-47 does not activates ROS, inhibits the UPS, or affects the cell cycle.
RUN-47 modulates proteasome activity, autophagy, and increase cell survival under proteotoxic and oxidative stress.
RUN-47 acts upstream of NRF1, stabilizing NRF1, and this stabilization effectively leads to NRF1 transcriptional activation.
RUN-47 prevents protein aggregate formation in cells, reduces the formation of Lewy body-like aggregates in SH-SY5Y cells overexpressing SNCA-EGFP.
RUN-47 activates SKN-1 A/NRF1 in C. elegans, prevents aggregate formation, and reduces sensitivity to juglone-induced oxidative stress in vivo.
RUN-47 also reduces the formation of α-synuclein aggregates in C. elegans, demonstrates a significant protective effect against juglone-induced lethal oxidative stress.