biKEAP1 is a potent, unique bivalent inhibitor of BTB-containing E3 ligase KEAP1 dimer with ITC Kd of 10.4 nM, promotes the dimerization of KEAP1 and binds to KEAP1 in a bivalent fashion, instantly activates NRF2 by promoting the release of NRF2 from the KEAP1 dimer.
biKEAP1 exhibits of antioxidant response element (ARE) induction EC50 of 98.72 nM.
biKEAP1 promotes the formation of KEAP1 dimer in vitro.
biKEAP1 activates the NRF2 pathway and enhanced the antioxidative capacity in RAW264.7 cells.
biKEAP1 activates NRF2-mediated cytoprotective system and alleviates cellular inflammatory conditions much more quickly and potently.
biKEAP1 can simultaneously target the CUL3-KEAP1 dimer complex and engage the cellular KEAP1 dimer to directly release the sequestered NRF2 protein, rather than inactivating KEAP1 to induce the accumulation of newly synthesized NRF2, leading to an instant NRF2 activation.
biKEAP1 exhibits promising therapeutic potential in viral/bacterial infections-induced inflammatory cytokine storm.