NFE2L2

Summary

NFE2L2 (NFE2 like bZIP transcription factor 2, HGNC:7782) is a protein-coding gene on chromosome 2q31.2, encoding Nuclear factor erythroid 2-related factor 2 (Q16236). Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reac…. In precision oncology, NFE2L2 Mutation confers sensitivity to Sapanisertib in Lung Squamous Cell Carcinoma (CIViC Level B); 1 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 12.3% of cell lines).

This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene.

Source: NCBI Gene 4780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency, developmental delay, and hypohomocysteinemia (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 404 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 9 cancer types
• Cancer dependency (DepMap): dependent in 12.3% of screened cell lines
• Transcription factor: yes — 217 downstream targets (CollecTRI)
• MANE Select transcript: NM_006164

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7782
Approved symbol	NFE2L2
Name	NFE2 like bZIP transcription factor 2
Location	2q31.2
Locus type	gene with protein product
Status	Approved
Aliases	NRF2, NRF-2
Ensembl gene	ENSG00000116044
Ensembl biotype	protein_coding
OMIM	600492
Entrez	4780

Gene structure

Transcript identifiers

Ensembl transcripts: 67 — 54 protein_coding, 8 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000397062, ENST00000397063, ENST00000421929, ENST00000423513, ENST00000446151, ENST00000448782, ENST00000458603, ENST00000462023, ENST00000464747, ENST00000477534, ENST00000586532, ENST00000588123, ENST00000699220, ENST00000699223, ENST00000699224, ENST00000699264, ENST00000699265, ENST00000699296, ENST00000699297, ENST00000699298, ENST00000699299, ENST00000699300, ENST00000699301, ENST00000699302, ENST00000699303, ENST00000699304, ENST00000699305, ENST00000699306, ENST00000699307, ENST00000699308, ENST00000699309, ENST00000699327, ENST00000699328, ENST00000699329, ENST00000699330, ENST00000699331, ENST00000699332, ENST00000699342, ENST00000699343, ENST00000699344, ENST00000699345, ENST00000699346, ENST00000699347, ENST00000699348, ENST00000699349, ENST00000699350, ENST00000699351, ENST00000699352, ENST00000699353, ENST00000699404, ENST00000699405, ENST00000699406, ENST00000699407, ENST00000699408, ENST00000699409, ENST00000699410, ENST00000699411, ENST00000699412, ENST00000699413, ENST00000699414, ENST00000699431, ENST00000699432, ENST00000699433, ENST00000699434, ENST00000699435, ENST00000894418, ENST00000950353

RefSeq mRNA: 8 — MANE Select: NM_006164 NM_001145412, NM_001145413, NM_001313900, NM_001313901, NM_001313902, NM_001313903, NM_001313904, NM_006164

CCDS: CCDS42782, CCDS46457, CCDS46458, CCDS92903, CCDS92904

Canonical transcript exons

ENST00000397062 — 5 exons

Exon	Start	End
ENSE00002816418	177230308	177232008
ENSE00002852995	177232392	177232583
ENSE00002953704	177233250	177233339
ENSE00003494657	177234005	177234271
ENSE00003976197	177264532	177264727

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.8404 / max 520.6183, expressed in 1824 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31988	36.7019	1819
31982	5.4211	1310
32000	4.9258	1513
31983	4.7333	1423
31987	3.5993	1389
31984	2.9923	823
31985	0.6455	333
31989	0.2417	83
31990	0.1795	53
31993	0.1351	38

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	99.57	gold quality
pharyngeal mucosa	UBERON:0000355	99.37	gold quality
oral cavity	UBERON:0000167	99.32	gold quality
bronchial epithelial cell	CL:0002328	99.18	gold quality
esophagus squamous epithelium	UBERON:0006920	99.17	gold quality
pylorus	UBERON:0001166	99.10	gold quality
cardia of stomach	UBERON:0001162	99.06	gold quality
pericardium	UBERON:0002407	99.04	gold quality
jejunal mucosa	UBERON:0000399	99.00	gold quality
penis	UBERON:0000989	99.00	gold quality
germinal epithelium of ovary	UBERON:0001304	98.97	gold quality
upper leg skin	UBERON:0004262	98.90	gold quality
mammalian vulva	UBERON:0000997	98.83	gold quality
gingiva	UBERON:0001828	98.83	gold quality
tongue	UBERON:0001723	98.78	gold quality
epithelium of esophagus	UBERON:0001976	98.78	gold quality
body of tongue	UBERON:0011876	98.76	gold quality
esophagus mucosa	UBERON:0002469	98.75	gold quality
tongue squamous epithelium	UBERON:0006919	98.71	gold quality
gingival epithelium	UBERON:0001949	98.67	gold quality
superior surface of tongue	UBERON:0007371	98.65	gold quality
squamous epithelium	UBERON:0006914	98.63	gold quality
epithelium of bronchus	UBERON:0002031	98.62	gold quality
bronchus	UBERON:0002185	98.62	gold quality
parietal pleura	UBERON:0002400	98.59	gold quality
seminal vesicle	UBERON:0000998	98.53	gold quality
palpebral conjunctiva	UBERON:0001812	98.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.45	gold quality
nasal cavity mucosa	UBERON:0001826	98.43	gold quality
lower esophagus mucosa	UBERON:0035834	98.41	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	3326.93
E-GEOD-131882	yes	3317.78
E-MTAB-9543	yes	1586.10
E-GEOD-93593	yes	6.89
E-CURD-135	no	695.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

217 targets.

Target	Regulation
ABCB11	Unknown
ABCC1	Unknown
ABCC2
ABCC3
ABCC4	Activation
ABCG2	Unknown
ACHE
ADRA1D
AHR	Unknown
AKR1B1	Unknown
AKR1B10
AKR1C1
AKR1C2	Activation
AKT1
ALS2
AOX1
APC
AQP1
AR
ATF3	Unknown
ATF4	Activation
BACH1
BCL2
BCL2L1
BCL2L11
BGLAP	Unknown
BRCA1	Activation
CACNA1C
CALCA
CASP1

JASPAR motifs

Motif	Name	Family
MA0150.1	NFE2L2	Jun-related

JASPAR matrix evidence (PMIDs): PMID:17916232

Upstream regulators (CollecTRI, top): AHR, ATF4, BRAF, COQ7, CTCF, ESR1, EZH2, HIF1A, KLF2, KRAS, MT3, MYC, NCOA3, NCOR2, NFE2L2, NFKB, SIRT5, TP53

miRNA regulators (miRDB)

63 targeting NFE2L2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Nrf2 is involved in antioxidant response element mediated transcriptional activation in response to acrolein exposure (PMID:12084617)
• Nfe2l2 is involved in the regulation of Ucp1 by cAMP-mediated signaling. (PMID:12084707)
• Keap1 dimerization causes Nrf2 sequestration (PMID:12145307)
• expression inhibited laminar flow-induced NQO1 promoter activation in endothelial cells (PMID:12370194)
• Nrf2 is required for the induction of ferritin in response to polycyclic aromatic xenobiotics and chemopreventive agents and may also play a role in basal transcription of both ferritin H and L (PMID:12435735)
• Nrf2 is degraded by the ubiquitin-dependent pathway and phosphorylation of Nrf2 leads to an increase in its stability and subsequent transactivation activity (PMID:12446695)
• phosphorylation of serine 40 is necessary for nuclear factor((erythroid-derived 2)like 2(Nrf2) release from Inhibitor of Nrf2(INrf2) (PMID:12947090)
• This review describes the extensive analysis of the mechanisms involved in the stress response element (StRE)/Nrf2 transcription factor pathway for heme oxygenase-1 gene regulation. (PMID:14529549)
• nf-e2 activated TXAS promoter in a dose-dependent manner. (PMID:14565864)
• different segments of Nrf2 transactivation domain have different transactivation potential and different MAPKs have differential effects on Nrf2 transcriptional activity (PMID:15020583)
• Data show that Keap1 associates with the N-terminal region of Cullin 3 through the IVR domain and promotes the ubiquitination of Nrf2 in cooperation with the Cullin 3-Roc1 complex. (PMID:15282312)
• importance of examining the link between NRF2 polymorphisms and other oxidative stress-related diseases (PMID:15358217)
• Nrf2 stabilization by pharmacological modulation or adenovirus-mediated Nrf2 overexpression might be viable strategies to prevent a wide-spectrum of oxidative stress-related neuronal cell injuries. (PMID:15525690)
• Keap1 negatively regulates Nrf2 function in part by targeting Nrf2 for ubiquitination by the CUL3-ROC1 ligase and subsequent degradation by the proteasome (PMID:15601839)
• Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants (PMID:15734732)
• Nrf2 canonical nuclear export signal may help decipher the mechanisms governing nuclear localization and subsequent transcriptional activation of Nrf2-mediated cytoprotective genes. (PMID:15917227)
• results suggest that pro-atherogenic oscillatory flow inhibits Nrf2 activity at the DNA binding step, thereby suppressing athero-protective gene expression and hence predisposing the blood vessels to the formation of atherosclerosis. (PMID:15917255)
• Data suggest that some antioxidants may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx by Nrf2 binding. (PMID:15923610)
• chlorogenic acid stimulates Nrf2, inhibits activator protein-1, NF-kappaB, and MAPKs and induces phase 2 detoxifying enzyme activity (PMID:15944151)
• activation of PKC, p38(MAPK), JNK, ERK1/2, and Nrf2 by oxidized LDL in human smooth muscle cells leads to HO-1 induction, constituting an adaptive response against oxidative injury that can be ameliorated by vitamin C (PMID:15964514)
• stabilization of Nrf2 in cells under stress represents the central regulatory response mediated by mechanisms that interfere with its interaction with Keap1, leading to the induction of antioxidant enzymes important to maintain cellular redox homeostasis (PMID:16000310)
• Component of the c-Ha-ras ARE/EpRE heterocomplex. We conclude that both internal bases and flanking sequences regulate nuclear protein recruitment and complex assembly. (PMID:16038408)
• nuclear factor-erythroid 2 p45-related factor 2 is a member of the Cap ’n’ Collar family of transcription factors that binds to the antioxidant response elements (PMID:16092930)
• alpha-lipoic acid induces HO-1 expression in THP-1 monocytic cells via Nrf2 and p38 (PMID:16123320)
• These findings suggest a role for FAC1 in apoptosis following release of Nrf2 from Keap1 in response to oxidative stress. (PMID:16137655)
• Lipopolysaccharide induces heme oxygenase 1 mRNA and protein expression in monocytic cells via activation of the transcription factor Nrf2. (PMID:16177082)
• Nrf2 expression significantly increases IL-8 mRNA levels and protein secretion in primary human kidney mesangial cells, aortic endothelial cells and malignant cell lines. (PMID:16220540)
• p38 MAPK and Nrf2 have roles in phenolic acid-induced P-form phenol sulfotransferase expression in human hepatoma HepG2 cells (PMID:16308312)
• These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD. (PMID:16325767)
• These data identify the Nrf2/ARE pathway as an endogenous atheroprotective system for antioxidant protection and suppression of redox-sensitive inflammatory genes. (PMID:16339837)
• AKR1C1 promoter has an antioxidant response element which is bound by NRF2 in a ChiP analysis. (PMID:16478829)
• a structural basis is provided for the loss of Keap1 function and gain of Nrf2 function in lung cancer cells (PMID:16507366)
• Treatment of Hep-G2 cells with Nrf2-specific RNAi reduced Nrf2 & NQO2 gene expression & tBHQ induction. Nrf2 associates with JunD, binds to ARE at nucleotide -1433, & regulates human NQO2 gene expression & induction in response to antioxidants. (PMID:16545679)
• Nrf2, through up-regulation of glutamate-cysteine ligase and increase of GSH levels, protects against CYP2E1-dependent AA toxicity (PMID:16551616)
• GSK3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2 (PMID:16551619)
• This study thus manifests that a clear set of rules pertaining to the cis-acting element determine whether a given Maf-recognition elements preferentially associates with MafG homodimer or with MafG:Nrf2 heterodimer. (PMID:16716189)
• Nrf2 may be self-sufficient to sense and transduce oxidative signals into the nucleus, consequently initiating antioxidant gene transcription (PMID:16790425)
• Data demonstrate that induction of NADPH-dependent quinone oxidoreductase (Aor) activity by 15-Deoxy-Delta12,14-prostaglandin J2 is markedly attenuated in mouse embryonic fibroblasts that overexpress rat Aor. (PMID:16857669)
• These results thus demonstrate that BRG1, through the facilitation of Z-DNA formation and subsequent recruitment of RNA polymerase II, is critical in Nrf2-mediated inducible expression of HO-1. (PMID:16923960)
• Nrf2-mediated heme oxygenase-1 overexpression confers resistance to apoptosis induction by EGCG (PMID:16950787)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfe2l2a	ENSDARG00000042824
mus_musculus	Nfe2l2	ENSMUSG00000015839
rattus_norvegicus	Nfe2l2	ENSRNOG00000001548

Paralogs (3): NFE2L3 (ENSG00000050344), NFE2L1 (ENSG00000082641), NFE2 (ENSG00000123405)

Protein

Protein identifiers

Nuclear factor erythroid 2-related factor 2 — Q16236 (reviewed: Q16236)

Alternative names: Nuclear factor, erythroid derived 2, like 2

All UniProt accessions (30): A0A8V8TN14, A0A8V8TN31, A0A8V8TN40, A0A8V8TN41, A0A8V8TN51, A0A8V8TN85, A0A8V8TND9, A0A8V8TNI6, A0A8V8TNJ6, A0A8V8TNM0, A0A8V8TNM5, A0A8V8TNQ8, A0A8V8TNS1, A0A8V8TPA8, A0A8V8TPC8, A0A8V8TPF0, Q16236, A0A8V8TPF4, A0A8V8TPI5, A0A8V8TPL6, A0A8V8TPM0, A0A8V8TPN5, A0A8V8TPT8, A0A8V8TPX0, A0A8V8TQ20, C9J0Y1, C9J1A8, H7C498, K7EIW5, K7ER33

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes. The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes. The NFE2L2/NRF2 pathway is also activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival following endoplasmic reticulum stress. May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region. Also plays an important role in the regulation of the innate immune response and antiviral cytosolic DNA sensing. It is a critical regulator of the innate immune response and survival during sepsis by maintaining redox homeostasis and restraint of the dysregulation of pro-inflammatory signaling pathways like MyD88-dependent and -independent and TNF signaling. Suppresses macrophage inflammatory response by blocking pro-inflammatory cytokine transcription and the induction of IL6. Binds to the proximity of pro-inflammatory genes in macrophages and inhibits RNA Pol II recruitment. The inhibition is independent of the NRF2-binding motif and reactive oxygen species level. Represses antiviral cytosolic DNA sensing by suppressing the expression of the adapter protein STING1 and decreasing responsiveness to STING1 agonists while increasing susceptibility to infection with DNA viruses. Once activated, limits the release of pro-inflammatory cytokines in response to human coronavirus SARS-CoV-2 infection and to virus-derived ligands through a mechanism that involves inhibition of IRF3 dimerization. Also inhibits both SARS-CoV-2 replication, as well as the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism.

Subunit / interactions. Heterodimer; heterodimerizes with small Maf proteins. Interacts (via the bZIP domain) with MAFG and MAFK; required for binding to antioxidant response elements (AREs) on DNA. Interacts with KEAP1; the interaction is direct and promotes ubiquitination by the BCR(KEAP1) E3 ubiquitin ligase complex. Forms a ternary complex with PGAM5 and KEAP1. Interacts with EEF1D at heat shock promoter elements (HSE). Interacts via its leucine-zipper domain with the coiled-coil domain of PMF1. Interacts with CHD6; involved in activation of the transcription. Interacts with ESRRB; represses NFE2L2 transcriptional activity. Interacts with MOTS-c, a peptide produced by the mitochondrially encoded 12S rRNA MT-RNR1; the interaction occurs in the nucleus following metabolic stress. (Microbial infection) Interacts with herpes virus 8 protein LANA1.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Widely expressed. Highest expression in adult muscle, kidney, lung, liver and in fetal muscle.

Post-translational modifications. Ubiquitinated in the cytoplasm by the BCR(KEAP1) E3 ubiquitin ligase complex leading to its degradation. In response to oxidative stress, electrophile metabolites, such as sulforaphane, modify KEAP1, leading to inhibit activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and activity. In response to autophagy, the BCR(KEAP1) complex is inactivated. Phosphorylated by EIF2AK3/PERK following unfolded protein response (UPR), promoting dissociation from its cytoplasmic inhibitor KEAP1, followed by its translocation into the nucleus. Phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus. Acetylation at Lys-596 and Lys-599 increases nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence. Glycation impairs transcription factor activity by preventing heterodimerization with small Maf proteins. Deglycation by FN3K restores activity.

Disease relevance. Immunodeficiency, developmental delay, and hypohomocysteinemia (IMDDHH) [MIM:617744] An early onset multisystem disorder characterized by immunodeficiency, recurrent infections, developmental delay, poor growth, intellectual disability, and hypohomocysteinemia. Some patients manifest congenital cardiac defects. IMDDHH inheritance pattern is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by cell derived metabolites including itaconate and fumarate. (Microbial infection) Transcription factor activity on antioxidant target genes is significantly inhibited by SARS coronavirus-2/SARS-COV-2.

Domain organisation. The ETGE motif, and to a lower extent the DLG motif, mediate interaction with KEAP1.

Induction. Down-regulated by ENC1 via a proteasomal ubiquitin-independent protein catabolic process.

Similarity. Belongs to the bZIP family. CNC subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16236-1	1	yes
Q16236-2	2
Q16236-3	3

RefSeq proteins (8): NP_001138884, NP_001138885, NP_001300829, NP_001300830, NP_001300831, NP_001300832, NP_001300833, NP_006155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004826	bZIP_Maf	Domain
IPR004827	bZIP	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR046347	bZIP_sf	Homologous_superfamily
IPR047167	NFE2-like	Family

Pfam: PF03131

UniProt features (50 total): mutagenesis site 9, sequence variant 7, glycosylation site 6, region of interest 5, modified residue 4, sequence conflict 4, helix 4, compositionally biased region 3, splice variant 2, short sequence motif 2, chain 1, domain 1, turn 1, strand 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
2FLU	X-RAY DIFFRACTION	1.5
9T8Y	X-RAY DIFFRACTION	1.79
4IFL	X-RAY DIFFRACTION	1.8
8HZ8	X-RAY DIFFRACTION	1.81
7K2A	X-RAY DIFFRACTION	1.9
5WFV	X-RAY DIFFRACTION	1.91
7K2K	X-RAY DIFFRACTION	1.98
7K2E	X-RAY DIFFRACTION	2.03
8EJR	X-RAY DIFFRACTION	2.08
7K2C	X-RAY DIFFRACTION	2.11
9T95	X-RAY DIFFRACTION	2.15
7K28	X-RAY DIFFRACTION	2.15
3ZGC	X-RAY DIFFRACTION	2.2
7K29	X-RAY DIFFRACTION	2.2
7K2D	X-RAY DIFFRACTION	2.21
7X5E	X-RAY DIFFRACTION	2.3
7X5G	X-RAY DIFFRACTION	2.3
7K2B	X-RAY DIFFRACTION	2.31
6T7V	X-RAY DIFFRACTION	2.6
7X5F	X-RAY DIFFRACTION	2.6
8EJS	X-RAY DIFFRACTION	2.82
2LZ1	SOLUTION NMR
7O7B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16236-F1	61.72	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 40, 215, 596, 599

Glycosylation sites (6): 462, 472, 487, 499, 569, 574

Mutagenesis-validated functional residues (9):

Position	Phenotype
79–82	abolished interaction with keap1.
80	loss of interaction with keap1.
82	abolished interaction with keap1.
462	loss of function; when associated with a-472; a-487; a-499; a-569 and a-587.
472	loss of function; when associated with a-462; a-487; a-499; a-569 and a-587.
487	loss of function; when associated with a-462; a-472; a-499; a-569 and a-587.
499	loss of function; when associated with a-462; a-472; a-487; a-569 and a-587.
569	loss of function; when associated with a-462; a-472; a-487; a-499 and a-587.
587	loss of function; when associated with a-462; a-472; a-487; a-499 and a-569.

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9707587	Regulation of HMOX1 expression and activity
R-HSA-9707616	Heme signaling
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2
R-HSA-9762114	GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2
R-HSA-9818025	NFE2L2 regulating TCA cycle genes
R-HSA-9818026	NFE2L2 regulating inflammation associated genes
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes
R-HSA-9818028	NFE2L2 regulates pentose phosphate pathway genes
R-HSA-9818030	NFE2L2 regulating tumorigenic genes
R-HSA-9818032	NFE2L2 regulating MDR associated enzymes
R-HSA-9818035	NFE2L2 regulating ER-stress associated genes
R-HSA-9818749	Regulation of NFE2L2 gene expression
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9943962	CHD6, CHD7, CHD8, CHD9 subfamily
R-HSA-1643685	Disease
R-HSA-2262752	Cellular responses to stress
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9679506	SARS-CoV Infections
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 736 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_WOUND_HEALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_COAGULATION, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_STEM_CELL_DIFFERENTIATION

GO Biological Process (55): response to ischemia (GO:0002931), regulation of transcription by RNA polymerase II (GO:0006357), inflammatory response (GO:0006954), response to oxidative stress (GO:0006979), gene expression (GO:0010467), proteasomal ubiquitin-independent protein catabolic process (GO:0010499), positive regulation of gene expression (GO:0010628), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of neuron projection development (GO:0010976), protein ubiquitination (GO:0016567), positive regulation of blood coagulation (GO:0030194), T cell differentiation (GO:0030217), endoplasmic reticulum unfolded protein response (GO:0030968), cellular response to oxidative stress (GO:0034599), PERK-mediated unfolded protein response (GO:0036499), cellular response to glucose starvation (GO:0042149), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of blood vessel endothelial cell migration (GO:0043536), regulation of innate immune response (GO:0045088), cell redox homeostasis (GO:0045454), positive regulation of angiogenesis (GO:0045766), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of embryonic development (GO:0045995), aflatoxin catabolic process (GO:0046223), positive regulation of D-glucose import across plasma membrane (GO:0046326), digestive tract development (GO:0048565), cellular response to methionine (GO:0061431), response to caloric restriction (GO:0061771), cellular response to hydrogen peroxide (GO:0070301), cellular response to copper ion (GO:0071280), cellular response to tumor necrosis factor (GO:0071356), cellular response to hypoxia (GO:0071456), cellular response to xenobiotic stimulus (GO:0071466), cellular response to fluid shear stress (GO:0071498), cellular response to laminar fluid shear stress (GO:0071499), reactive oxygen species metabolic process (GO:0072593), negative regulation of ferroptosis (GO:0110076), integrated stress response signaling (GO:0140467), negative regulation of cellular response to hypoxia (GO:1900038)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein domain specific binding (GO:0019904), ubiquitin protein ligase binding (GO:0031625), sequence-specific DNA binding (GO:0043565), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515)

GO Cellular Component (12): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), mediator complex (GO:0016592), protein-DNA complex (GO:0032993), ciliary basal body (GO:0036064), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Nuclear events mediated by NFE2L2	9
Post-translational protein modification	1
SARS-CoV Infections	1
Cytoprotection by HMOX1	1
Cellular responses to stress	1
Cellular response to chemical stress	1
KEAP1-NFE2L2 pathway	1
Regulation of PD-L1(CD274) expression	1
CHD chromatin remodelers	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
response to stress	2
regulation of DNA-templated transcription	2
proteasomal protein catabolic process	2
intracellular membrane-bounded organelle	2
cytoplasm	2
microtubule organizing center	2
nuclear protein-containing complex	2
transcription by RNA polymerase II	1
defense response	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
protein modification by small protein conjugation	1
blood coagulation	1
regulation of blood coagulation	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
lymphocyte differentiation	1
T cell activation	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
response to oxidative stress	1
cellular response to chemical stress	1
ER-nucleus signaling pathway	1
endoplasmic reticulum unfolded protein response	1
integrated stress response signaling	1
cellular response to starvation	1
ubiquitin-dependent protein catabolic process	1
positive regulation of endothelial cell migration	1

Protein interactions and networks

STRING

4120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFE2L2	KEAP1	Q14145	999
NFE2L2	MAF	O75444	997
NFE2L2	MAFG	O15525	993
NFE2L2	HMOX1	P09601	960
NFE2L2	MAFF	Q9ULX9	947
NFE2L2	NQO1	P15559	941
NFE2L2	PPARGC1A	Q9UBK2	940
NFE2L2	MAFK	O60675	933
NFE2L2	GCLC	P48506	930
NFE2L2	PMF1	Q6P1K2	906
NFE2L2	GCLM	P48507	906
NFE2L2	A0A087WT04	A0A087WT04	905
NFE2L2	CUL3	Q13618	902
NFE2L2	ATF4	P18848	845
NFE2L2	PPARG	P37231	831

IntAct

321 interactions, top by confidence:

A	B	Type	Score
NFE2L2	KEAP1	psi-mi:“MI:0915”(physical association)	0.980
KEAP1	NFE2L2	psi-mi:“MI:0915”(physical association)	0.980
KEAP1	NFE2L2	psi-mi:“MI:0407”(direct interaction)	0.980
NFE2L2	KEAP1	psi-mi:“MI:0914”(association)	0.980
KEAP1	NFE2L2	psi-mi:“MI:0914”(association)	0.980
MAFG	NFE2L2	psi-mi:“MI:0915”(physical association)	0.940
NFE2L2	MAFG	psi-mi:“MI:0915”(physical association)	0.940
MAFK	NFE2L2	psi-mi:“MI:0915”(physical association)	0.810
NFE2L2	MAFK	psi-mi:“MI:0915”(physical association)	0.810
NFE2L2	MAFF	psi-mi:“MI:0915”(physical association)	0.770
NFE2L2	ATF4	psi-mi:“MI:2364”(proximity)	0.730
NFE2L2	ATF4	psi-mi:“MI:0914”(association)	0.730
ATF4	NFE2L2	psi-mi:“MI:0914”(association)	0.730
NFE2L2	ATF4	psi-mi:“MI:0915”(physical association)	0.730
TNNT1	NFE2L2	psi-mi:“MI:0915”(physical association)	0.670
NFE2L2	TNNT1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (513): NFE2L2 (Affinity Capture-Western), MAPK7 (Affinity Capture-Western), MAPK7 (Reconstituted Complex), HDAC1 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), NFE2L2 (Biochemical Activity), NFE2L2 (Affinity Capture-MS), TNNT1 (Two-hybrid), WAC (Two-hybrid), TCF20 (Co-localization), NFE2L2 (Biochemical Activity), NFE2L2 (Biochemical Activity), NFE2L2 (Affinity Capture-MS), UBC (Affinity Capture-Western)

ESM2 similar proteins: A1YG22, A2T7L5, B8XIA5, O54968, P01106, P01108, P01109, P01110, P06171, P06295, P06646, P09416, P0C0N8, P0C0N9, P10395, P12523, P12525, P15171, P21438, P22555, P23583, P23999, P35805, P49032, P49033, P49709, P52160, P68271, P68272, Q05404, Q16236, Q17103, Q28350, Q28566, Q29031, Q2HJ27, Q5NUA6, Q60795, Q64210, Q6DFC8

Diamond homologs: A5D7E9, O14867, O54968, P20482, P34707, P97302, P97303, Q07279, Q14494, Q16236, Q16621, Q5EAD3, Q5NUA6, Q5RA25, Q5ZL67, Q60795, Q61985, Q6AYT2, Q9BYV9, Q9Y4A8, Q9WTM4, A0JN76, A1L2U9, A1YPR0, B1WAZ8, B1WBU4, D4A2K4, E0CZ16, E1B932, F1LZ52, F1LZF0, F1MBP6, O15062, O43167, O43298, O88282, O88939, O93567, O95198, O95365

SIGNOR signaling

64 interactions.

A	Effect	B	Mechanism
KEAP1	down-regulates	NFE2L2	binding
NFE2L2	“up-regulates quantity by expression”	TBXAS1	“transcriptional regulation”
NFE2L2	“down-regulates quantity by repression”	GCLC	“transcriptional regulation”
NFE2L2	“down-regulates quantity by repression”	GSTA1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	KRT16	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	TXN	“transcriptional regulation”
BTG2	“up-regulates activity”	NFE2L2	binding
NFE2L2	“up-regulates quantity by expression”	CAT	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	SOD2	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
NFE2L2	up-regulates	Proliferation
NFE2L2	down-regulates	Apoptosis
NFE2L2	“up-regulates quantity by expression”	NQO1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	HMOX1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	GCLC	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	GSTA1	“transcriptional regulation”
NFE2L2	down-regulates	Cell_death
NFE2L2	up-regulates	Metastasis
NFE2L2	“up-regulates quantity”	HMOX1	“transcriptional regulation”
KEAP1	“down-regulates quantity”	NFE2L2	ubiquitination
SIRT5	“up-regulates quantity by expression”	NFE2L2	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	PXDN	“transcriptional regulation”
NFE2L2	up-regulates	Purine_biosynthesis
ROS	up-regulates	NFE2L2
NFE2L2	“up-regulates quantity by expression”	G6PD	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	PGD	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	TKT	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	TALDO1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	PPAT	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Nuclear events mediated by NFE2L2	5	31.7×	8e-05
Regulation of PD-L1(CD274) transcription	8	16.4×	1e-05
Cellular response to chemical stress	6	16.2×	2e-04
Interferon Signaling	6	13.6×	3e-04
Cellular Senescence	5	13.0×	2e-03
Regulation of TP53 Activity	5	12.5×	2e-03
Transcriptional regulation of granulopoiesis	5	11.8×	2e-03
KEAP1-NFE2L2 pathway	5	11.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	5	53.2×	4e-06
liver development	6	20.2×	4e-05
response to endoplasmic reticulum stress	5	12.6×	2e-03
transforming growth factor beta receptor signaling pathway	5	12.0×	3e-03
transcription by RNA polymerase II	10	10.7×	4e-06
regulation of cell cycle	9	10.2×	2e-05
positive regulation of gene expression	9	5.3×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 9 cancer types — BLCA, CESC, ESCA, HCC, HNSC, LUSC, NSCLC, PRCC, UCEC.

Clinical variants and AI predictions

ClinVar

404 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	222
Likely benign	115
Benign	33

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
376466	NM_006164.5(NFE2L2):c.235G>A (p.Glu79Lys)	Pathogenic
445148	NM_006164.5(NFE2L2):c.239C>A (p.Thr80Lys)	Pathogenic
445149	NM_006164.5(NFE2L2):c.241G>A (p.Gly81Ser)	Pathogenic
1333190	NM_006164.5(NFE2L2):c.246A>T (p.Glu82Asp)	Likely pathogenic

SpliceAI

1125 predictions. Top by Δscore:

Variant	Effect	Δscore
2:177219031:TTTCA:T	acceptor_loss	1.0000
2:177219032:TTCA:T	acceptor_loss	1.0000
2:177219033:TCAGG:T	acceptor_loss	1.0000
2:177219035:A:AG	acceptor_gain	1.0000
2:177219035:AGGTA:A	acceptor_loss	1.0000
2:177219036:G:GA	acceptor_gain	1.0000
2:177219036:G:GT	acceptor_loss	1.0000
2:177219036:GGT:G	acceptor_gain	1.0000
2:177219036:GGTA:G	acceptor_gain	1.0000
2:177219036:GGTAA:G	acceptor_gain	1.0000
2:177219155:TGGTG:T	donor_gain	1.0000
2:177219156:GGTGG:G	donor_gain	1.0000
2:177219157:GTG:G	donor_gain	1.0000
2:177219158:TG:T	donor_gain	1.0000
2:177219159:GG:G	donor_gain	1.0000
2:177219159:GGT:G	donor_loss	1.0000
2:177219160:G:GG	donor_gain	1.0000
2:177219161:T:A	donor_loss	1.0000
2:177219239:A:AG	acceptor_gain	1.0000
2:177219241:TTTCA:T	acceptor_loss	1.0000
2:177219242:TTCA:T	acceptor_loss	1.0000
2:177219243:TCAG:T	acceptor_loss	1.0000
2:177219244:CAGG:C	acceptor_loss	1.0000
2:177219245:A:AG	acceptor_gain	1.0000
2:177219245:A:C	acceptor_loss	1.0000
2:177219245:AGGT:A	acceptor_gain	1.0000
2:177219245:AGGTG:A	acceptor_gain	1.0000
2:177219246:G:A	acceptor_loss	1.0000
2:177219246:G:GG	acceptor_gain	1.0000
2:177219246:GGT:G	acceptor_gain	1.0000

AlphaMissense

4042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:177231058:T:A	R515S	0.999
2:177231058:T:G	R515S	0.999
2:177231052:T:A	R517S	0.998
2:177231052:T:G	R517S	0.998
2:177231059:C:G	R515T	0.998
2:177231071:G:T	A511D	0.998
2:177231085:C:A	K506N	0.998
2:177231085:C:G	K506N	0.998
2:177231099:G:T	R502S	0.998
2:177230855:A:G	L583P	0.997
2:177230855:A:T	L583Q	0.997
2:177230900:A:G	L568P	0.997
2:177230933:A:G	L557P	0.997
2:177231029:A:G	L525P	0.997
2:177231051:T:C	K518E	0.997
2:177231074:G:T	A510D	0.997
2:177231079:T:A	K508N	0.997
2:177231079:T:G	K508N	0.997
2:177231082:A:C	N507K	0.997
2:177231082:A:T	N507K	0.997
2:177231089:C:T	G505D	0.997
2:177231091:C:A	R504S	0.997
2:177231091:C:G	R504S	0.997
2:177231094:C:A	R503S	0.997
2:177231094:C:G	R503S	0.997
2:177231098:C:G	R502P	0.997
2:177231160:G:C	F481L	0.997
2:177231160:G:T	F481L	0.997
2:177231161:A:G	F481S	0.997
2:177231162:A:G	F481L	0.997

dbSNP variants (sampled 300 via entrez): RS1000001894 (2:177241156 A>G), RS1000119440 (2:177237410 T>C), RS1000198755 (2:177265260 C>T), RS1000278935 (2:177230329 T>C,G), RS1000303075 (2:177259524 T>C), RS1000347882 (2:177244257 G>A), RS1000402416 (2:177237149 T>G), RS1000500889 (2:177266577 A>G), RS1000514273 (2:177249955 G>A,C), RS1000532292 (2:177264333 C>A), RS1000642925 (2:177264106 G>A), RS1000674106 (2:177256095 C>T), RS1000717328 (2:177265053 GAAACAGTTT>G), RS1000781093 (2:177244029 G>A), RS1000934802 (2:177233858 T>A,G)

Disease associations

OMIM: gene MIM:600492 | disease phenotypes: MIM:617744, MIM:211980, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency, developmental delay, and hypohomocysteinemia	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency, developmental delay, and hypohomocysteinemia	Limited	AD

Mondo (3): immunodeficiency, developmental delay, and hypohomocysteinemia (MONDO:0060591), lung cancer (MONDO:0008903), colorectal cancer (MONDO:0005575)

Orphanet (1): NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000750	Delayed speech and language development
HP:0001256	Mild intellectual disability
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001581	Recurrent skin infections
HP:0001609	Hoarse voice
HP:0001631	Atrial septal defect
HP:0001647	Bicuspid aortic valve
HP:0002315	Headache
HP:0002352	Leukoencephalopathy
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002750	Delayed skeletal maturation
HP:0002783	Recurrent lower respiratory tract infections
HP:0003388	Easy fatigability
HP:0003593	Infantile onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004322	Short stature
HP:0011342	Mild global developmental delay
HP:0011968	Feeding difficulties
HP:0012101	Decreased serum creatinine
HP:0020222	Hypohomocysteinemia
HP:0500152	Hypocystinemia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST007344_52	Estimated glomerular filtration rate	4.000000e-09
GCST008058_59	Estimated glomerular filtration rate	1.000000e-26
GCST008059_58	Estimated glomerular filtration rate	1.000000e-24
GCST008745_37	Estimated glomerular filtration rate in non-diabetics	2.000000e-10
GCST008747_10	Estimated glomerular filtration rate	4.000000e-11
GCST008747_57	Estimated glomerular filtration rate	2.000000e-14
GCST010002_405	Refractive error	1.000000e-70
GCST010242_276	HDL cholesterol levels	3.000000e-09
GCST90020024_1158	A body shape index	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1075094 (SINGLE PROTEIN), CHEMBL3038498 (PROTEIN-PROTEIN INTERACTION), CHEMBL5483087 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 546,784 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2107333	DIMETHYL FUMARATE	4	22,969
CHEMBL1200969	DUTASTERIDE	4	11,156
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1607	TOPOTECAN HYDROCHLORIDE	4	56,379
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	141,917
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL140	CURCUMIN	3	93,882
CHEMBL165	RESVERATROL	3	60,144
CHEMBL1762621	BARDOXOLONE METHYL	3	1,032
CHEMBL48802	SULFORAPHANE	3	7,981
CHEMBL1197091	HALOFUGINONE	2	1,000

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 3 curated evidence items; also 1 oncogenic, 1 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
NFE2L2 Mutation	Sapanisertib	Lung Squamous Cell Carcinoma	Sensitivity/Response	CIViC B	EID7425 +1
NFE2L2 Mutation OR KEAP1 Mutation OR CUL3 Mutation	Platinum Doublet	Lung Non-small Cell Carcinoma	Resistance	CIViC B	EID12558

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6721961	NFE2L2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Basic leucine zipper domain TFs

Binding affinities (BindingDB)

353 measured of 443 human assays (443 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-(4-chloro-1-methylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-7-ethoxy-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-4-ethyl-8-methyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-4-ethyl-7-methyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-7-ethoxy-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-[7-[[(4R)-8-chloro-4-ethyl-7-fluoro-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-4-ethyl-1,1-dioxo-8-(trifluoromethyl)-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[(4,4-dimethyl-1,1-dioxo-3H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[(1,1-dioxospiro[3H-pyrido[2,3-b][1,4,5]oxathiazepine-4,1’-cyclobutane]-2-yl)methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[(1,1-dioxospiro[3H-pyrido[2,3-b][1,4,5]oxathiazepine-4,3’-oxetane]-2-yl)methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]-3-(7-cyclopropyl-1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3S)-3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1H-inden-5-yl]-3-(7-cyclopropyl-1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3S)-3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[1,4-dimethyl-7-(trifluoromethoxy)benzotriazol-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-(7-methoxy-1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(7-chloro-1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-(7-cyano-1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[1,4-dimethyl-7-(trifluoromethyl)benzotriazol-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[1,4-dimethyl-7-(trifluoromethoxy)benzotriazol-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[7-(difluoromethoxy)-1,4-dimethylbenzotriazol-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[1-(2-hydroxy-2-methylpropyl)-4-methylbenzotriazol-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
ethyl 3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[4-methyl-1-(3-methylsulfonylpropyl)benzotriazol-5-yl]propanoate	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-(3,7-dimethyltriazolo[4,5-b]pyridin-6-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzothiophen-5-yl]-3-[4-methyl-1-(2,2,2-trifluoroethyl)benzotriazol-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
ethyl (3S)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoate	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(1,4-dimethyl-2,3-dihydrobenzotriazol-5-yl)-3-[7-[[(2R)-2-ethyl-5-methyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(1,4-dimethyl-2,3-dihydrobenzotriazol-5-yl)-3-[7-[[(2R,5S)-2,5-dimethyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(3,7-dimethyl-1,2-dihydrotriazolo[4,5-b]pyridin-6-yl)-3-[7-[[(2R)-2-ethyl-5-methyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
ethyl (3R)-3-(1,4-dimethyl-2,3-dihydrobenzotriazol-5-yl)-3-[7-[[(2R,5S)-2,5-dimethyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoate	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
ethyl (3R)-3-[7-[[(2R)-2-cyclopropyl-5-methyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]-3-(3,7-dimethyl-1,2-dihydrotriazolo[4,5-b]pyridin-6-yl)propanoate	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(5R)-5-methyl-7-oxospiro[5,6-dihydro-3H-pyrido[2,3-f][1,4]oxazepine-2,1’-cyclopropane]-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-(1,4-dimethylbenzotriazol-5-yl)-3-[4-[[(4R)-4-methyl-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl]methyl]-1H-indol-6-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-2,3-dihydro-1-benzofuran-5-yl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
3-[7-[[(4R)-8-chloro-4-ethyl-1,1-dioxo-3,4-dihydropyrido[2,3-b][1,4,5]oxathiazepin-2-yl]methyl]-1-benzofuran-5-yl]-3-(4-chloro-1-methylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
tert-butyl 6-[1-(7-cyclopropyl-1,4-dimethylbenzotriazol-5-yl)-3-ethoxy-3-oxopropyl]-4-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]indole-1-carboxylate	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3R)-3-(7-cyclopropyl-1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-2,3-dihydro-1H-inden-5-yl]propanoic acid	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
ethyl 3-(7-cyclopropyl-1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R,5S)-2-ethyl-5-methyl-3,5-dihydro-2H-pyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-2,3-dihydro-1-benzofuran-5-yl]propanoate	IC50	20 nM	US-20250092064: BENZOTRIAZOLE COMPOUND
(3S)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[[(2R)-2-ethyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND
(3S)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[(7-oxospiro[5,6-dihydro-3H-pyrido[2,3-f][1,4]oxazepine-2,1’-cyclopropane]-4-yl)methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND
(3R)-3-(1,4-dimethylbenzotriazol-5-yl)-3-[7-[(7-oxospiro[5,6-dihydro-3H-pyrido[2,3-f][1,4]oxazepine-2,1’-cyclopropane]-4-yl)methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND
(3R)-3-[7-[[(2R)-2-cyclopropyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND
(3S)-3-[7-[[(2R)-2-cyclopropyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND
(3R)-3-[7-[[(2R)-2-cyclopropyl-7-oxo-2,3,5,6-tetrahydropyrido[2,3-f][1,4]oxazepin-4-yl]methyl]-1-benzothiophen-5-yl]-3-(3,7-dimethyltriazolo[4,5-b]pyridin-6-yl)propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND
(3S)-3-(1,4-dimethylbenzotriazol-5-yl)-2,2-dimethyl-3-[7-[(7-oxospiro[5,6-dihydro-3H-pyrido[2,3-f][1,4]oxazepine-2,1’-cyclopropane]-4-yl)methyl]-1-benzothiophen-5-yl]propanoic acid	IC50	20 nM	US-20250296939: BENZOTHIOPHENE COMPOUND

ChEMBL bioactivities

1697 potent at pChembl≥5 of 2027 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Kd	0.01	nM	CHEMBL5759229
10.62	Kd	0.024	nM	CHEMBL5886931
10.39	Kd	0.041	nM	CHEMBL6052915
10.38	Kd	0.042	nM	CHEMBL6036229
10.10	Kd	0.079	nM	CHEMBL5945962
10.09	Kd	0.081	nM	CHEMBL5997320
10.09	Kd	0.081	nM	CHEMBL5920236
10.05	Kd	0.089	nM	CHEMBL5893955
9.92	Kd	0.12	nM	CHEMBL5996288
9.90	Kd	0.127	nM	CHEMBL5915606
9.80	Kd	0.16	nM	CHEMBL5789875
9.79	Kd	0.162	nM	CHEMBL5765112
9.76	Kd	0.174	nM	CHEMBL5881215
9.73	Kd	0.188	nM	CHEMBL5823251
9.62	Kd	0.24	nM	CHEMBL5756145
9.58	Kd	0.264	nM	CHEMBL5818820
9.56	Kd	0.273	nM	CHEMBL5956739
9.56	Kd	0.278	nM	CHEMBL6033425
9.47	Kd	0.34	nM	CHEMBL5964184
9.38	Kd	0.42	nM	CHEMBL6000717
9.29	Kd	0.518	nM	CHEMBL5815214
9.01	Kd	0.97	nM	CHEMBL6054981
9.00	Ki	1	nM	CHEMBL3237245
9.00	Kd	1	nM	CHEMBL5998600
8.99	Kd	1.02	nM	CHEMBL5904165
8.97	Kd	1.08	nM	CHEMBL5966649
8.96	Kd	1.1	nM	CHEMBL5824789
8.96	Kd	1.1	nM	CHEMBL5864191
8.96	Kd	1.09	nM	CHEMBL5966874
8.96	Kd	1.1	nM	CHEMBL5838878
8.92	Kd	1.2	nM	CHEMBL5748784
8.92	Kd	1.2	nM	CHEMBL5783798
8.92	Kd	1.2	nM	CHEMBL6025266
8.92	Kd	1.19	nM	CHEMBL5776238
8.92	Kd	1.19	nM	CHEMBL5948517
8.92	Kd	1.19	nM	CHEMBL6022430
8.91	Kd	1.24	nM	CHEMBL6065860
8.90	Kd	1.26	nM	CHEMBL5859607
8.89	Kd	1.3	nM	CHEMBL5757170
8.89	Kd	1.28	nM	CHEMBL5900035
8.89	Kd	1.29	nM	CHEMBL5747464
8.89	Kd	1.3	nM	CHEMBL3819587
8.85	Kd	1.4	nM	CHEMBL5806480
8.85	Kd	1.4	nM	CHEMBL5971865
8.82	Ki	1.5	nM	CHEMBL5429390
8.82	Kd	1.5	nM	CHEMBL5815084
8.82	Kd	1.5	nM	CHEMBL5980289
8.82	Kd	1.51	nM	CHEMBL6052870
8.80	Kd	1.6	nM	CHEMBL6024876
8.80	Kd	1.6	nM	CHEMBL5901077

PubChem BioAssay actives

832 with measured affinity, of 4809 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-[3-(1,3-dioxoisoindol-2-yl)propyl]naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0001	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2088407: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) assessed as inhibition constant by TR-FRET assay	ki	0.0010	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-phenylsulfanylnaphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0015	uM
2-[[3-(carboxymethoxy)-4-[carboxymethyl-(4-methylphenyl)sulfonylamino]naphthalen-1-yl]-(4-methylphenyl)sulfonylamino]acetic acid	2088408: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0019	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-(3-morpholin-4-yl-3-oxopropyl)naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0020	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-[4-(1,3-dioxoisoindol-2-yl)phenyl]naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0021	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-phenylnaphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0024	uM
8,8-dimethyl-4-(4-methyl-3-pyridinyl)-9-oxo-1-oxa-4-azaspiro[5.5]undec-10-ene-10-carbonitrile	1828011: Modulation of Keap1-Nrf2 protein-protein interaction in human U2OS cells assessed as inhibition of Keap1 by PathHunter assay	ec50	0.0025	uM
6-chloro-5’,5’-dimethyl-6’-oxospiro[1H-2-benzofuran-3,3’-cyclohexene]-1’-carbonitrile	1828011: Modulation of Keap1-Nrf2 protein-protein interaction in human U2OS cells assessed as inhibition of Keap1 by PathHunter assay	ec50	0.0029	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-(4-cyanophenyl)naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0031	uM
8,8-dimethyl-9-oxo-4-pyridin-3-yl-1-oxa-4-azaspiro[5.5]undec-10-ene-10-carbonitrile	1828011: Modulation of Keap1-Nrf2 protein-protein interaction in human U2OS cells assessed as inhibition of Keap1 by PathHunter assay	ec50	0.0031	uM
4-(3-fluoro-4-pyridinyl)-8,8-dimethyl-9-oxo-1-oxa-4-azaspiro[5.5]undec-10-ene-10-carbonitrile	1828011: Modulation of Keap1-Nrf2 protein-protein interaction in human U2OS cells assessed as inhibition of Keap1 by PathHunter assay	ec50	0.0032	uM
2-[[3-(3-amino-3-oxopropyl)-4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0042	uM
8,8-dimethyl-4-(5-methyl-3-pyridinyl)-9-oxo-1-oxa-4-azaspiro[5.5]undec-10-ene-10-carbonitrile	1828011: Modulation of Keap1-Nrf2 protein-protein interaction in human U2OS cells assessed as inhibition of Keap1 by PathHunter assay	ec50	0.0045	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-[3-oxo-3-(propan-2-ylamino)propyl]naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0046	uM
2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-3-(4-methoxyphenyl)naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0049	uM
(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]pentanedioic acid	1204220: Binding affinity to Keap1/Nrf2 complex (unknown origin) by ITC method	kd	0.0050	uM
8,8-dimethyl-9-oxo-4-pyridin-2-yl-1-oxa-4-azaspiro[5.5]undec-10-ene-10-carbonitrile	1828011: Modulation of Keap1-Nrf2 protein-protein interaction in human U2OS cells assessed as inhibition of Keap1 by PathHunter assay	ec50	0.0058	uM
2-[3-(carboxymethoxy)-4-[carboxymethyl-(4-methylphenyl)sulfonylamino]-N-(4-methylphenyl)sulfonylanilino]acetic acid	2088408: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0064	uM
N-[4-[2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl(2H-tetrazol-5-ylmethyl)amino]naphthalen-1-yl]-N-(2H-tetrazol-5-ylmethyl)-2,3-dihydro-1,4-benzodioxine-6-sulfonamide	1755203: Inhibition of recombinant human KEAP1 Kelch domain (321 to 609 residues) expressed in Escherichia coli BL21 (DE3)pLysS cells interaction with FITC-9mer Nrf2 (unknown origin) incubated for 30 mins under shaking condition by TR-FRET assay	ic50	0.0072	uM
2-[[4-[carboxymethyl-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)sulfonyl]amino]naphthalen-1-yl]-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)sulfonyl]amino]acetic acid	1755203: Inhibition of recombinant human KEAP1 Kelch domain (321 to 609 residues) expressed in Escherichia coli BL21 (DE3)pLysS cells interaction with FITC-9mer Nrf2 (unknown origin) incubated for 30 mins under shaking condition by TR-FRET assay	ic50	0.0089	uM
3-[1,4-bis[carboxymethyl-(4-methylphenyl)sulfonylamino]naphthalen-2-yl]propanoic acid	2088407: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) assessed as inhibition constant by TR-FRET assay	ki	0.0091	uM
(3S)-3-(1-ethyl-4-methylbenzotriazol-5-yl)-3-[2-(2,3,5,6-tetramethylbenzoyl)-3,4-dihydro-1H-isoquinolin-7-yl]propanoic acid	1651208: Activation of Nrf2 in human spinal cord astrocytes assessed as increase in glutathione level after 20 hrs	ec50	0.0092	uM
3-[1,4-bis[(2-amino-2-oxoethyl)-(4-methoxyphenyl)sulfonylamino]naphthalen-2-yl]propanoic acid	2008554: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) preincubated for 30 mins followed by Terbium labeled anti-His antibody addition for 30 mins prior to fluorescein labeled-9mer Nrf2 peptide addition and measured after 60 mins by TR-FRET assay	ki	0.0093	uM
1-[3-[3-[(1S)-1-cyclohexylethoxy]phenyl]phenyl]-5-[(1R,2R)-2-(1-methyltriazol-4-yl)cyclopropyl]pyrazole-4-carboxylic acid	1354589: Inhibition of Keap1 kelch domain (unknow origin)/Nrf2-ETGE peptide (unknown origin) interaction by fluorescence polarization assay	ic50	0.0100	uM
1-[3-[3-[(2R)-2-butylpyrrolidine-1-carbonyl]phenyl]phenyl]-5-cyclopropylpyrazole-4-carboxylic acid	1354595: Inhibition of full length Flag/His-tagged Keap1 kelch domain (unknown origin)/full length Avi-tagged Nrf2 (unknown origin) interaction after 2.25 hrs by TR-FRET assay	ic50	0.0100	uM
methyl (4aR,5S,6aR,6bS,8aR,12aS,14aR,14bR)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-3,4,4a,5,6,7,8,8a,14a,14b-decahydro-1H-picene-5-carboxylate	1707643: Activation of Nrf2 (unknown origin) expressed in human U2OS cells co-expressing Keap1 assessed as increase in Nrf2 nuclear translocation incubated for 6 hrs under dark condition by pathhunter assay	ec50	0.0100	uM
4-methoxy-N-[4-[(4-methoxyphenyl)sulfonyl-(2H-tetrazol-5-ylmethyl)amino]naphthalen-1-yl]-N-(2H-tetrazol-5-ylmethyl)benzenesulfonamide	1755203: Inhibition of recombinant human KEAP1 Kelch domain (321 to 609 residues) expressed in Escherichia coli BL21 (DE3)pLysS cells interaction with FITC-9mer Nrf2 (unknown origin) incubated for 30 mins under shaking condition by TR-FRET assay	ic50	0.0108	uM
3-(7-methoxy-1-methylbenzotriazol-5-yl)-3-[4-methyl-3-[[(4R)-4-methyl-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl]methyl]phenyl]propanoic acid	1588008: Activation of Nrf2 in human BEAS2B cells assessed as increase in NQO1 enzymatic activity measured after 48 hrs by MTT assay	ec50	0.0110	uM
2-[[4-[carboxymethyl-[4-(1,3-dioxoisoindol-2-yl)phenyl]sulfonylamino]naphthalen-1-yl]-[4-(1,3-dioxoisoindol-2-yl)phenyl]sulfonylamino]acetic acid	1755203: Inhibition of recombinant human KEAP1 Kelch domain (321 to 609 residues) expressed in Escherichia coli BL21 (DE3)pLysS cells interaction with FITC-9mer Nrf2 (unknown origin) incubated for 30 mins under shaking condition by TR-FRET assay	ic50	0.0115	uM
(2S)-2-[2,5-bis[carboxymethyl-(4-methylphenyl)sulfonylamino]phenoxy]propanoic acid	2088408: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0116	uM
(3S)-3-(7-methoxy-1-methylbenzotriazol-5-yl)-3-[4-methyl-3-[[(4R)-4-methyl-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl]methyl]phenyl]propanoic acid	1307876: Inhibition of KEAP1/NRF2 interaction in human BEAS2B cells assessed as induction of NQO1 specific activity incubated for 48 hrs measured on day 4 post dosing by MTT reduction assay	ec50	0.0120	uM
2-[(4-acetamidophenyl)sulfonyl-[4-[(4-acetamidophenyl)sulfonyl-(carboxymethyl)amino]naphthalen-1-yl]amino]acetic acid	1632947: Inhibition of Keap1 Kelch domain/FITC-9mer Nrf2 (unknown origin) interaction after 30 mins by fluorescence polarization assay	ic50	0.0134	uM
2-[[4-[carboxymethyl-(4-methylphenyl)sulfonylamino]-3-[(4-fluorophenyl)methoxy]naphthalen-1-yl]-(4-methylphenyl)sulfonylamino]acetic acid	1867745: Inhibition of His-tagged Keap1 kelch domain/Nrf2 (unknown origin) protein-protein interaction using FITC-LDEETGEFL-NH2 peptide as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by TR-FRET assay	ic50	0.0142	uM
N-[4-[[4-[(4-acetamidophenyl)sulfonyl-(2H-tetrazol-5-ylmethyl)amino]naphthalen-1-yl]-(2H-tetrazol-5-ylmethyl)sulfamoyl]phenyl]acetamide	1632947: Inhibition of Keap1 Kelch domain/FITC-9mer Nrf2 (unknown origin) interaction after 30 mins by fluorescence polarization assay	ic50	0.0158	uM
2-[[4-[carboxymethyl-(4-methylphenyl)sulfonylamino]naphthalen-1-yl]-(4-methylphenyl)sulfonylamino]acetic acid	1239359: Inhibition of Keap1 Kelch domain-Nrf2 ETGE (unknown origin) protein-protein interaction incubated for 30 mins by fluorescence polarization competition assay	ic50	0.0181	uM
1-[(E)-2-(benzenesulfonyl)ethenyl]-4-pyridin-3-yltetrazol-5-one	2038660: Activation of Nrf2 in human PathHunter U2OS Keap1-Nrf2 cells assessed as Nrf2 nuclear translocation by chemiluminescent assay	ec50	0.0200	uM
N-(2-methoxy-4-methylphenyl)sulfonyl-2-(3-methoxyphenyl)-2-[4-[(4-methoxyphenyl)sulfonyl-[2-[(4-methoxyphenyl)sulfonylamino]-2-oxoethyl]amino]-2,3-dihydroindol-1-yl]acetamide	1918108: Inhibition of Keap1 kelch domain to Nrf2 (unknown origin) protein-protein interaction	ic50	0.0220	uM
(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S,3R)-2-[[(2S)-4-carboxy-2-[[(2S)-1-[(2S)-3-carboxy-2-(octadecanoylamino)propanoyl]pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]butanoyl]amino]-4-methylpentanoic acid	1324993: Inhibition of Keap1/Nrf2 (unknown origin) interaction assessed as displacement of FITC-betaAla-DEETGEF-OH from Keap1 Kelch domain after 1 hr by FITC-based FP assay	ic50	0.0220	uM
7-bromo-6-chloro-3-[3-(3-hydroxypiperidin-2-yl)-2-oxopropyl]quinazolin-4-one	2130478: Inhibition of NRF2 in human KYSE-70 cells	ic50	0.0223	uM
2-[(4-methoxyphenyl)sulfonyl-[4-[(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]amino]acetamide	2087900: Inhibition of human Keap1 KELCH domain (321 to 609 residues) expressed in Escherichia coli BL21 DE3 pLysS cells/Nrf2 (unknown origin) protein-protein interaction preincubated with Keap1 for 1 hr followed by Nrf2 addition and measured after 1 hr by fluorescence polarization assay	ic50	0.0257	uM
3-chloro-2-[(E)-2-(2-chlorophenyl)sulfonylethenyl]pyridine	1707643: Activation of Nrf2 (unknown origin) expressed in human U2OS cells co-expressing Keap1 assessed as increase in Nrf2 nuclear translocation incubated for 6 hrs under dark condition by pathhunter assay	ec50	0.0260	uM
2-[(4-methoxyphenyl)sulfonyl-[4-[(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]amino]acetic acid	1248054: Inhibition of Keap1 (unknown origin) interaction to Nrf2	ec50	0.0286	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-4-carboxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid	1204219: Binding affinity to Keap1/Nrf2 complex (unknown origin) by fluorescence polarization assay	kd	0.0287	uM
methyl (1R,2S,3R,6R,8R,13S,14R,15R,16S,17S)-10,15,16-trihydroxy-9,13-dimethyl-3-(3-methylbut-2-enoyloxy)-4,11-dioxo-5,18-dioxapentacyclo[12.5.0.01,6.02,17.08,13]nonadec-9-ene-17-carboxylate	1634200: Inhibition of NRF2 in human MDA-MB-231 cells harboring ARE-GFP-Luc assessed as reduction in ARE-luciferase activity after 16 hrs by firefly luciferase reporter gene assay	ic50	0.0292	uM
3-(7-methoxy-1-methylbenzotriazol-5-yl)-3-[4-methyl-3-[(4-methyl-1,1-dioxo-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-2-yl)methyl]phenyl]propanoic acid	1588008: Activation of Nrf2 in human BEAS2B cells assessed as increase in NQO1 enzymatic activity measured after 48 hrs by MTT assay	ec50	0.0300	uM
3-chloro-2-[(E)-2-(2-fluorophenyl)sulfonylethenyl]pyridine	1707643: Activation of Nrf2 (unknown origin) expressed in human U2OS cells co-expressing Keap1 assessed as increase in Nrf2 nuclear translocation incubated for 6 hrs under dark condition by pathhunter assay	ec50	0.0300	uM
3-chloro-2-[(E)-2-[(4-methoxy-2-pyridinyl)sulfonyl]ethenyl]pyridine	2017838: Activation of Nrf2 in human U2OS cells co-expressing Keap1 assessed as induction of Nrf2 nuclear translocation incubated for 6 hrs by PathHunter chemiluminescence based analysis	ec50	0.0300	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-4-carboxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid	1204219: Binding affinity to Keap1/Nrf2 complex (unknown origin) by fluorescence polarization assay	kd	0.0301	uM
2-[3-(carboxymethoxy)-4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]-N-(4-methoxyphenyl)sulfonylanilino]acetic acid	2088407: Inhibition of Keap1-Nrf2 protein-protein interaction (unknown origin) assessed as inhibition constant by TR-FRET assay	ki	0.0302	uM

CTD chemical–gene interactions

719 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects localization, increases activity, increases abundance, decreases reaction, increases reaction (+13 more)	51
sulforaphane	affects localization, increases activity, increases phosphorylation, increases reaction, affects cotreatment (+11 more)	45
Acetylcysteine	affects binding, increases abundance, affects expression, decreases reaction, increases reaction (+8 more)	43
2-tert-butylhydroquinone	affects binding, decreases reaction, increases ubiquitination, decreases response to substance, increases secretion (+10 more)	34
Particulate Matter	affects localization, increases activity, affects cotreatment, increases response to substance, affects expression (+8 more)	24
Resveratrol	increases reaction, decreases expression, affects localization, affects response to substance, affects binding (+13 more)	23
Hydrogen Peroxide	increases expression, affects localization, increases phosphorylation, affects reaction, increases activity (+9 more)	23
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases activity, increases expression, increases phosphorylation, decreases expression, affects cotreatment (+4 more)	19
Arsenic Trioxide	decreases reaction, decreases expression, affects binding, increases expression, increases response to substance (+7 more)	19
Cisplatin	increases response to substance, decreases phosphorylation, affects activity, increases expression, decreases stability (+12 more)	19
Paraquat	affects localization, increases localization, decreases activity, increases expression, affects binding (+8 more)	19
Quercetin	decreases ubiquitination, affects reaction, affects cotreatment, decreases activity, increases expression (+12 more)	18
Cadmium Chloride	affects localization, affects binding, increases reaction, decreases expression, increases expression (+5 more)	18
Lipopolysaccharides	increases expression, increases reaction, affects cotreatment, affects binding, decreases expression (+4 more)	17
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects cotreatment, decreases expression, increases reaction, affects binding, decreases reaction (+7 more)	16
Benzo(a)pyrene	affects response to substance, increases abundance, decreases response to substance, affects localization, increases reaction (+7 more)	14
Arsenic	decreases expression, increases abundance, increases expression, increases methylation, increases reaction (+6 more)	13
bisphenol A	decreases reaction, increases expression, decreases expression, decreases phosphorylation, increases activity (+7 more)	12
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases expression, decreases abundance, affects cotreatment (+4 more)	12
Cadmium	decreases reaction, increases expression, increases activity, increases localization, affects localization (+3 more)	11
Glucose	decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment (+1 more)	11
Tobacco Smoke Pollution	increases activity, increases expression, increases reaction, decreases expression, decreases reaction (+6 more)	11
Reactive Oxygen Species	increases activity, increases reaction, affects reaction, decreases reaction, increases abundance (+2 more)	11
arsenite	decreases reaction, affects binding, increases localization, increases secretion, affects expression (+10 more)	10
Acrolein	decreases reaction, decreases response to substance, increases response to substance, decreases expression, increases activity (+7 more)	10
hydroquinone	increases reaction, increases ubiquitination, affects binding, affects reaction, increases activity (+7 more)	9
Vehicle Emissions	increases stability, decreases reaction, decreases expression, increases abundance, increases activity (+6 more)	9
Curcumin	affects localization, increases expression, increases reaction, affects binding, decreases response to substance (+5 more)	9
Glutathione	affects reaction, increases abundance, increases activity, increases expression, affects localization (+4 more)	9
Plant Extracts	affects localization, decreases reaction, affects reaction, increases reaction, affects cotreatment (+5 more)	9

ChEMBL screening assays

861 unique, capped per target: 812 binding, 49 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1112689	Functional	Induction of NrF2 in human HepG2 cells at 10 uM after 6 hrs by ARE-luciferase reporter gene assay	Enhanced Nrf2-dependent induction of glutathione in mouse embryonic fibroblasts by isoselenocyanate analog of sulforaphane. — Bioorg Med Chem Lett
CHEMBL2027137	Binding	Induction of Nrf2 transcriptional activity in human MCF7 cells antioxidant response element at 5 uM after 18 hrs by luciferase reporter gene assay relative to 2,5-DHC	A synthetic chalcone as a potent inducer of glutathione biosynthesis. — J Med Chem

Cellosaurus cell lines

27 cell lines: 14 cancer cell line, 7 transformed cell line, 3 spontaneously immortalized cell line, 2 induced pluripotent stem cell, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8LH	Abcam HCT 116 NFE2L2 KO	Cancer cell line	Male
CVCL_B8ZH	Abcam MCF-7 NFE2L2 KO	Cancer cell line	Female
CVCL_B9VR	Abcam HeLa NFE2L2 KO	Cancer cell line	Female
CVCL_D0I5	MHHi001-A-6	Induced pluripotent stem cell	Female
CVCL_D0I6	MHHi001-A-7	Induced pluripotent stem cell	Female
CVCL_D1TQ	Abcam U-87MG NFE2L2 KO	Cancer cell line	Male
CVCL_D7VQ	Ubigene A-549 NFE2L2 KO	Cancer cell line	Male
CVCL_D9L7	Ubigene HEK293 NFE2L2 KO	Transformed cell line	Female
CVCL_E0UM	Ubigene Hep G2 NFE2L2 KO	Cancer cell line	Male
CVCL_E1D4	Ubigene THP-1 NFE2L2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00440960	PHASE4	COMPLETED	Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic
NCT00492843	PHASE4	TERMINATED	Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00675168	PHASE4	UNKNOWN	Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice
NCT00712647	PHASE4	COMPLETED	Carotene and Retinol Efficacy Trial
NCT00747773	PHASE4	COMPLETED	Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung
NCT01060137	PHASE4	COMPLETED	Fentanyl Matrix in Lung Cancer Pain
NCT01381627	PHASE4	UNKNOWN	Safety Evaluation of Dexmedetomidine for EBUS-TBNA
NCT01741506	PHASE4	COMPLETED	Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer
NCT02246023	PHASE4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02275702	PHASE4	COMPLETED	Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients
NCT02346318	PHASE4	UNKNOWN	The Randomized Controlled Clinical Trial of Kushen Injection
NCT02476526	PHASE4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02490059	PHASE4	COMPLETED	Ultrathin Bronchoscopy for Solitary Pulmonary Nodules
NCT02504801	PHASE4	UNKNOWN	Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD
NCT02869789	PHASE4	COMPLETED	An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers
NCT03302221	PHASE4	WITHDRAWN	Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound
NCT03313544	PHASE4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03394222	PHASE4	COMPLETED	Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV
NCT03570645	PHASE4	COMPLETED	Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block
NCT03571126	PHASE4	UNKNOWN	Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer
NCT03642457	PHASE4	TERMINATED	Efficacy Between Serratus Plane Block And Local Infiltration In Vats
NCT04145570	PHASE4	COMPLETED	A Single-Dose,ComparativeBioavailability Study ofTwo Formulations ofErlotinib150mgTabletsunderFastingConditions
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04613284	PHASE4	UNKNOWN	Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC
NCT05463913	PHASE4	RECRUITING	Lung Nodule Detection Using Ultra-long FOV PET/CT
NCT05521789	PHASE4	RECRUITING	Erector Spinae Block for Thoracic Surgery
NCT05525338	PHASE4	RECRUITING	Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
NCT05663242	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06105801	PHASE4	RECRUITING	EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
NCT06276933	PHASE4	NOT_YET_RECRUITING	A Study of Camrelizumab Combined With Chemotherapy ± Thalidomide in First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT06646471	PHASE4	RECRUITING	PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00002550	PHASE3	COMPLETED	Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
NCT00002583	PHASE3	COMPLETED	Vinorelbine + Cisplatin or No Further Therapy in Non-small Cell Lung Cancer That Has Been Surgically Removed
NCT00002623	PHASE3	COMPLETED	Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer