Potential Applications of NRF2 Inhibitors in Cancer Therapy

Table 1

Compound	Target	Tumor type/cell lines	Effect	Ref no.
AEM1	Sirt2, NRF2	NSCLC/A549	Decreases NRF2 transcriptional activity	[269]
ML385	Neh1 domain of NRF2	NSCLC/A549	Impairs the DNA interaction of the MAFG-NRF2 complex	[25]
Procyanidins from CCE	IGF1R	NSCLC/A549	Promotes proteasome-independent NRF2 degradation through IGF1R phosphorylation	[271–273]
Luteolin	NRF2	NSCLC/A549	Decreases NRF2 mRNA and protein levels	[274, 275]
Trigonelline	NRF2 import system	PDAC/Panc-1, MiaPaca2; PAC/Colo357	Decreases the nuclear levels of NRF2	[276]
Brusatol	Overall protein translation	NSCLC/A549; TNBC/MDA-MB-231; PDAC/Panc1; PAC/BxPC3, PATU-8988; CRC/HCT116; melanoma/A537; AML/THP1, HL60	Promotes NRF2 degradation	[17, 236, 282–285, 287, 291, 292]
Chrysin	Hexokinase2, ERK1/2, NF-κB, NRF2	HCC/Bel-7402ADM; glioblastoma/U87	Decreases NRF2 mRNA and protein content; decreases NRF2 nuclear translocation	[293, 294]
Apigenin	PI3K/Akt	HCC/Bel-7402ADM	Decreases NRF2 mRNA and protein content	[266]
Oridonin	PPARγ, NF-κB, NRF2, JNK	Osteosarcoma/MG-63, HOS; BC/MDA-MB-231, MCF7; CRC/Hct116; DLBCL/SUDHL2 and 4, OCl-Ly-3 and 8	Decreases NRF2 nuclear translocation	[296–299]
Convallatoxin	NRF2	NSCLC/A549	Promotes GSK-3β/β-TrCP-dependent NRF2 degradation	[301]
Honokiol	NF-κB, NRF2	Burkitt’s lymphoma/Raji; T-all/MOLT-4	Decreases NRF2 expression	[302]
Berberine	c-Myc, NRF2	BAC/BT-474, AU-565	Promotes GSK-3β/β-TrCP-dependent NRF2 degradation	[307]
Parthenolide	NF-κB, JNK, STAT	TNBC/MDA-MB-231; BC/MCF7	Decreases NRF2 expression	[310–314]
Wogonin	MAPKs, NF-κB, p53, cMyc, PI3K/Akt, DNA-PKcs, STAT3, NRF2	BC/MCF-7; HCC/HepG2; CML/K562-A02; HNC/AMC-HN4R and -HN9R	Decreases NRF2 content at the transcriptional level; increases KEAP1 levels	[315–319]