Evidence has shown their capability to increase the expression of NRF2 target genes in cellular and in vivo models of chronic obstructive pulmonary disease (COPD) [298], and to interfere with the direct PPI between KEAP1 and NRF2 or the PPI between KEAP1 and CUL3 [299, 300]. Here, CUL3 is linked to chronic obstructive pulmonary disease.