ARP-4922

ARP-4922 is an orally bioavailable small molecule that acts as a degrader of NRF2, a transcription factor involved in the regulation of cytoprotective responses to oxidative and electrophilic stress. Unlike traditional approaches that inhibit NRF2 through KEAP1, ARP-4922 induces proteasome-dependent degradation of NRF2 even in the absence of functional KEAP1. This mechanism leads to downregulation of known NRF2 target genes such as SLC7A11 and NQO1. Preclinical studies have demonstrated that ARP-4922 results in sustained tumor regression in mouse xenograft models with KEAP1-mutant non-small cell lung cancer (NSCLC). The drug is being developed by Arpeggio Biosciences for the treatment of cancers characterized by aberrant activation of the NRF2 pathway, particularly those with KEAP1 mutations[1][2].