NRF2의 억제제

https://blog.naver.com/sunsailor/222558306034

Potential Applications of NRF2 Inhibitors in Cancer Therapy

NRF2에 대한 억제 효과가 있는 천연 화합물

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

 

기타 억제 가능성이 있는 화합물

​NRF2의 활성화를 촉진함에도 항종양 활성을 나타낼 수 있는 성분도 있습니다.

​

- EGCG

- Rubia cordifolia L. (Rubiaceae)

- mollugin

- DHEA

​

오프라벨 약물

 

Drug                         Previous                            type/cell lines                                                     Effect                        Ref.

 

ATRA, RAR-α agonists	APL treatment; neuroblastoma treatment; skin disorders	BC/MCF-7; AML/HL60, THP-1; APL/NB4, NB4-R2; NB/HTLA-230; GBM/U251; OC/A2780 CSC	Decreases NRF2 binding to ARE sites; decreases NRF2 nuclear translocation	[347–350]
PHA-767491	Cdc7/CDK9 inhibitor	PDAC/PANC-1, Capan-1; HCC/HepG2	Decreases NRF2 nuclear translocation and activity	[351]
Sorafenib	Multi-Tyrosine kinase inhibitor; antiangiogenic therapy	CRC/DLD-1, HCT116; TC/FTC133, BC-PAP, 8505C; RC/ACHN, 786-O; CRC/DLD-1; HCC/HepG2, BEL7402-5FU, HuH-7; BC/MCF7, MDA-MB-231; NSCLC/CALU-3	Decreases NRF2 expression and nuclear translocation	[352]
Auranofin	Rheumatoid arthritis	NSCLC/Calu-3, Calu-6, H522	Decreases NRF2 activation	[353]
Clobetasol Propionate	Skin disorders	NSCLC/A549, H2228	Decreases NRF2 nuclear accumulation and promotes β-TrCP-dependent NRF2 degradation	[354]
Camptothecin	Topoisomerase inhibitor; chemotherapy	HCC/HepG2, SMMC-7721; NSCLC/A549	Decreases NRF2 expression	[23]
Valproic acid	Histone deacetylase inhibitor; epilepsy and seizure disorders; chemosensitizer	BC/MCF7; TC/BCPAP, TCP1, BHP10-3	Decreases NRF2 nuclear content	[355]
Metformin	Antidiabetic drug	BC/MCF-7; CRC/HT-29; EC/RL95–2, Spec-2, Ishikawa; HCC/HepG2; NSCLC/A549; CC/HeLa	Decreases NRF2 mRNA and protein content; decreases NRF2 expression	[356–361]
Isoniazid	Antitubercular agent	HCC/HepG2	Decreases NRF2 nuclear translocation	[3

 Oxidative Medicine and Cellular Longevity Volume 2019, Article ID 8592348, 34페이지 https://doi.org/10.1155/2019/8592348