TXNRD1

Summary

TXNRD1 (thioredoxin reductase 1, HGNC:12437) is a protein-coding gene on chromosome 12q23.3, encoding Thioredoxin reductase 1, cytoplasmic (Q16881). Reduces disulfide protein thioredoxin (Trx) to its dithiol-containing form. It is a selective cancer dependency (DepMap: 55.5% of cell lines).

The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes an ubiquitously expressed, cytosolic form of TrxR, which functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing, primarily at the 5’ end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis.

Source: NCBI Gene 7296 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 130 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 55.5% of screened cell lines
• MANE Select transcript: NM_001093771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12437
Approved symbol	TXNRD1
Name	thioredoxin reductase 1
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	TXNR, GRIM-12, Trxr1, TXNR1
Ensembl gene	ENSG00000198431
Ensembl biotype	protein_coding
OMIM	601112
Entrez	7296

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000503506, ENST00000524698, ENST00000525265, ENST00000525566, ENST00000526006, ENST00000526207, ENST00000526266, ENST00000526390, ENST00000526580, ENST00000526691, ENST00000526950, ENST00000527335, ENST00000527688, ENST00000529546, ENST00000529751, ENST00000529784, ENST00000531689, ENST00000531691, ENST00000534282

RefSeq mRNA: 7 — MANE Select: NM_001093771 NM_001093771, NM_001261445, NM_001261446, NM_003330, NM_182729, NM_182742, NM_182743

CCDS: CCDS53820, CCDS53821, CCDS53823, CCDS58274

Canonical transcript exons

ENST00000525566 — 17 exons

Exon	Start	End
ENSE00001508558	104334237	104334332
ENSE00001508559	104331534	104331641
ENSE00001508560	104327515	104327671
ENSE00001508563	104321091	104321316
ENSE00001508564	104319470	104319585
ENSE00001508565	104318913	104319055
ENSE00001508566	104315777	104315896
ENSE00002174074	104215779	104215893
ENSE00003534976	104326347	104326423
ENSE00003543334	104313245	104313317
ENSE00003549212	104339139	104339273
ENSE00003605762	104311290	104311412
ENSE00003618326	104251527	104251678
ENSE00003619457	104258019	104258079
ENSE00003651189	104325337	104325429
ENSE00003653995	104288931	104289040
ENSE00003849636	104348353	104350307

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 145.5473 / max 3523.4075, expressed in 1823 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127730	115.8332	1821
127733	16.1865	1642
127729	10.5827	1759
127732	1.2785	589
127739	0.9691	554
127734	0.2940	154
127725	0.2687	118
127731	0.0997	39
127726	0.0349	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.42	gold quality
islet of Langerhans	UBERON:0000006	99.00	gold quality
adrenal tissue	UBERON:0018303	99.00	gold quality
right adrenal gland	UBERON:0001233	98.29	gold quality
right adrenal gland cortex	UBERON:0035827	98.28	gold quality
left adrenal gland	UBERON:0001234	98.13	gold quality
adrenal gland	UBERON:0002369	97.95	gold quality
adrenal cortex	UBERON:0001235	97.89	gold quality
left adrenal gland cortex	UBERON:0035825	97.86	gold quality
right coronary artery	UBERON:0001625	97.49	gold quality
pericardium	UBERON:0002407	97.23	gold quality
left coronary artery	UBERON:0001626	97.17	gold quality
endometrium epithelium	UBERON:0004811	97.17	gold quality
coronary artery	UBERON:0001621	96.96	gold quality
nasal cavity epithelium	UBERON:0005384	96.60	gold quality
descending thoracic aorta	UBERON:0002345	96.51	gold quality
thoracic aorta	UBERON:0001515	96.16	gold quality
smooth muscle tissue	UBERON:0001135	96.12	gold quality
right lung	UBERON:0002167	96.10	gold quality
ascending aorta	UBERON:0001496	96.05	gold quality
gall bladder	UBERON:0002110	96.01	gold quality
cartilage tissue	UBERON:0002418	95.90	gold quality
lower lobe of lung	UBERON:0008949	95.68	gold quality
type B pancreatic cell	CL:0000169	95.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.32	gold quality
bronchial epithelial cell	CL:0002328	95.26	gold quality
colonic epithelium	UBERON:0000397	95.23	gold quality
urinary bladder	UBERON:0001255	95.12	gold quality
right atrium auricular region	UBERON:0006631	95.11	gold quality
upper lobe of lung	UBERON:0008948	95.08	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	798.15
E-HCAD-13	yes	7.00
E-MTAB-6386	no	358.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BACH1, CLOCK, DNMT1, NFE2L2, POU2F1

miRNA regulators (miRDB)

90 targeting TXNRD1, 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-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-590-3P	99.96	74.34	6478
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-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Methylseleninate is a substrate rather than an inhibitor of mammalian thioredoxin reductase. (PMID:11782468)
• Mutational analysis of human thioredoxin reductase 1. (PMID:11953436)
• identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein (PMID:12214272)
• selenoenzyme thioredoxin reductase is an important selenium-dependent ubiquinone reductase and may protect the cell from oxidative damage (PMID:12435734)
• Rapid induction of cell death by selenium-compromised thioredoxin reductase 1 but not by the fully active enzyme containing selenocysteine. (PMID:12574159)
• This protein is part of the host cytosolic translocation factor complex (CTF). ATP and the CTF are required for the cytoslic entry of the diphtheria toxin catalytic domain. (PMID:12668662)
• Thioredoxin reductase 1 is transcriptionally induced by elecrophiles via an antioxidant responsive element found in the promoter (PMID:12949356)
• Epithelial cells in normal, inflammatory, or neoplastic colonic mucosa do not expresss a relevant amount of TR1 mRNA and protein. (PMID:13679440)
• thioredoxin reductase is inhibited by 15-lipoxygenase-1 (PMID:15123685)
• In a tumor cell line TrxR1 promoter fragments linked to a luciferase reporter gene allowed identification of a defined promoter region as specifically responding to the phospholipid component of oxodozed low density lipoproteins. (PMID:15183196)
• TrxR1b is an important modulator of estrogen signaling (PMID:15199063)
• TRR-Trx and APE/Ref-1 cooperate in the control of basal p53 activity, but not in its induction by DNA-damage. (PMID:15824742)
• modification of TrxR by curcumin shifts it from an antioxidant to a prooxidant (PMID:15879598)
• Motexafin gadolinium induces enzymatic generation of reactive oxygen species by thioredoxin reductase and inhibits ribonucleotide reductase (PMID:16481328)
• glutathione disu binding at the N-terminal active site of thioredoxin reductase is electrostatically disfavoured (PMID:16750198)
• showed 3D model of one of active site in thioredoxin reductase 1 with bound thioredoxin (PMID:16977661)
• Overexpression of TrxR1 markedly increased glucocorticoid receptor activity in outer root sheath cells cultured in vitro. In addition, TrxR1 protected GR activity against H(2)O(2). (PMID:17382897)
• Results report the first crystal structure of human thioredoxin reductase 1 (Sec–>Cys) in complex with FAD and NADP(+) at a resolution of 2.8 A. (PMID:17512005)
• the Grx domain of TXNRD1_v3 localizes first in the emerging cell membrane protrusion and is then followed into the protrusions by actin and subsequently by tubulin (PMID:18042542)
• FMRP negatively regulates TXNRD1 translation. (PMID:18163424)
• Subsequent analysis demonstrated that TRXR1 suppresses hydrogen peroxide and inhibits apoptosis of RA synovial cells. (PMID:18187038)
• Therefore, TrxR1 inhibition alone was not sufficient to oxidize Trx1, suggesting that Trx1-independent pathways should be considered when evaluating pharmacological and toxicological mechanisms involving TrxR1 inhibition. (PMID:18267104)
• thioredoxin reductase is a prooxidant killer of cells in a pathway involving SecTRAPs (PMID:18382651)
• Significant 80% reduction for advanced colorectal adenoma risk for carriers of the variant allele at TDXRD1 IVS1-181C>G. (PMID:18483336)
• TR-1 acts as a negative regulator of Tat-dependent transcription. (PMID:18835810)
• Evidence for TXNRD1 as a modifier gene through association of familial amyotrophic lateral sclerosis (FALS) with the intronic SNPs rs6539137 and rs4630362. (PMID:18996185)
• TrxR1 activity in tumor cell extracts is significantly inhibited by green tea extract and (-)-epigallocatechin-3-gallate (PMID:19020731)
• Inhibition of thioredoxin reductase 1 by black tea and its constituents: implications for anticancer actions are reported. (PMID:19059456)
• This study suggests that TrxR1 enhances ROS generation, NF-kappaB activity and subsequent MCP-1 expression in endothelial cells, and may promote rather than prevent vascular endothelium from forming atherosclerotic plaque. (PMID:19555664)
• Observations underpin a likely critical antioxidant role for TrxR2 and TrxR1 in the endothelium. (PMID:19595745)
• Findings suggest that Trx and TrxR are multifunctional proteins that, in addition to modulating H(2)O(2) levels and transcription factor activity, aid ERalpha in regulating the expression of estrogen-responsive genes in target cells. (PMID:19620238)
• Using truncated versions of the protein we found that both the cytoplasmic filaments and the filopodia formation were exclusively dependent on the glutaredoxin domain of the protein. (PMID:19654027)
• High levels of expression in lung carcinoma cells modulate drug-specific cytotoxic efficacy (PMID:19766715)
• Caveolin 1 expression inhibits TrxR1-mediated cell transformation. (PMID:19820694)
• Results show the critical role of TxnRd1 in curcumin-mediated radiosensitization and suggest that TxnRd1 levels in tumors could have clinical value as a predictor of response to curcumin and radiotherapy. (PMID:20160040)
• TR1 and Trx1 interaction play key role in redox homoeostasis. (PMID:20536427)
• High expression of TXNRD1 is associated with breast cancer. (PMID:20584310)
• These results indicate the ability of TR1 to modulate the cytotoxic effects of selenium compounds in human lung cancer cells through mitochondrial dysfunction. (PMID:20920480)
• study reveals significant differences between TrxR1 and TrxR2 in substrate specificity and metal compound inhibition in vitro and in cells (PMID:21172426)
• Overexpression of TrxR1 could contribute to cancer progression and might be a potential molecular marker for therapy. (PMID:21206984)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Txnrd1	ENSMUSG00000020250
rattus_norvegicus	Txnrd1	ENSRNOG00000009088
drosophila_melanogaster	CG4199	FBGN0025628
drosophila_melanogaster	CG10700	FBGN0032754
caenorhabditis_elegans		WBGENE00017640

Paralogs (7): DLD (ENSG00000091140), GSR (ENSG00000104687), PYROXD1 (ENSG00000121350), AIFM1 (ENSG00000156709), AIFM3 (ENSG00000183773), TXNRD2 (ENSG00000184470), TXNRD3 (ENSG00000197763)

Protein

Protein identifiers

Thioredoxin reductase 1, cytoplasmic — Q16881 (reviewed: Q16881)

Alternative names: Gene associated with retinoic and interferon-induced mortality 12 protein, KM-102-derived reductase-like factor, Peroxidase TXNRD1, Thioredoxin reductase TR1

All UniProt accessions (10): A0A0B4J225, A0A182DWI3, E9PIR7, E9PIZ5, E9PKD3, E9PKI4, E9PLT3, E9PQI3, E9PRI8, Q16881

UniProt curated annotations — full annotation on UniProt →

Function. Reduces disulfide protein thioredoxin (Trx) to its dithiol-containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. A selenocysteine residue at the C-terminal active site is essential for catalysis. Also has reductase activity on hydrogen peroxide (H2O2). Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2. Enhances the transcriptional activity of the estrogen receptor ESR2 only. Mediates cell death induced by a combination of interferon-beta and retinoic acid.

Subunit / interactions. Homodimer. Interacts with HERC5. Interacts with ESR1 and ESR2.

Subcellular location. Cytoplasm Cytoplasm. Nucleus Cytoplasm.

Tissue specificity. Expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver.

Post-translational modifications. The N-terminus is blocked. ISGylated.

Cofactor. Binds 1 FAD per subunit.

Domain organisation. The N-terminal glutaredoxin domain does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins and has been found to be inactive in classical glutaredoxin assays.

Induction. Induced by estradiol or testosterone in HeLa cells. Induced by a combination of interferon-beta and retinoic acid (at protein level).

Miscellaneous. The thioredoxin reductase active site is a redox-active disulfide bond. A C-terminal selenocysteine residue is essential for catalytic activity. Minor isoform. Major isoform. The N-terminus of the sequence is processed into a mature form that lacks residues Met-151 and Asn-152 at the N-terminus.

Similarity. Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q16881-1	1, V, TXNRD1_v3	yes
Q16881-2	2, II, TXNRD1_v4
Q16881-3	3, III, TXNRD1_v5
Q16881-4	4, IV, TXNRD1_v2, TrxR1b
Q16881-5	5, I, TXNRD1_v1, TrxR1a
Q16881-6	6, VI
Q16881-7	7

RefSeq proteins (7): NP_001087240, NP_001248374, NP_001248375, NP_003321, NP_877393, NP_877419, NP_877420 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002109	Glutaredoxin	Domain
IPR004099	Pyr_nucl-diS_OxRdtase_dimer	Domain
IPR006338	Thioredoxin/glutathione_Rdtase	Family
IPR012999	Pyr_OxRdtase_I_AS	Active_site
IPR016156	FAD/NAD-linked_Rdtase_dimer_sf	Homologous_superfamily
IPR023753	FAD/NAD-binding_dom	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR046952	GSHR/TRXR-like	Family

Pfam: PF00462, PF02852, PF07992

Enzyme classification (BRENDA):

• EC 1.8.1.9 — thioredoxin-disulfide reductase (NADPH) (BRENDA: 75 organisms, 296 substrates, 269 inhibitors, 240 Km, 193 kcat entries)

Substrate kinetics (BRENDA)

59 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
THIOREDOXIN	0.0003–67.6	45
5,5’-DITHIOBIS(2-NITROBENZOIC ACID)	0.0186–172.4	36
NADPH	0.0004–4.5	33
THIOREDOXIN DISULFIDE	0.001–0.173	15
ARABIDOPSIS THALIANA THIOREDOXIN 3	0.0005–0.0543	10
HORDEUM VULGARE THIOREDOXIN 2	0.0007–0.06	10
NADH	0.011–0.736	9
DTNB	0.05–0.66	7
5,5’-DITHIO-BIS(2-NITROBENZOIC ACID)	0.032–11.9	6
LIPOAMIDE	0.0019–5.59	5
HORDEUM VULGARE THIOREDOXIN DISULFIDE H2	0.0009–0.0018	4
5-HYDROXY-1,4-NAPHTHOQUINONE	0.0023–0.0237	3
HORDEUM VULGARE THIOREDOXIN 2 MUTANT E86A	0.0004–0.0016	3
ESCHERICHIA COLI THIOREDOXIN	0.007–0.149	2
HORDEUM VULGARE THIOREDOXIN DISULFIDE H1	0.0011–0.0012	2

Catalyzed reactions (Rhea), 2 shown:

• H2O2 + NADPH + H(+) = NADP(+) + 2 H2O (RHEA:15173)
• [thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + NADPH + H(+) (RHEA:20345)

UniProt features (101 total): strand 24, binding site 18, helix 16, sequence conflict 13, splice variant 9, turn 8, modified residue 3, region of interest 2, chain 1, domain 1, non-standard amino acid 1, disulfide bond 1, cross-link 1, sequence variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3QFA	X-RAY DIFFRACTION	2.2
2ZZC	X-RAY DIFFRACTION	2.6
3QFB	X-RAY DIFFRACTION	2.6
2CFY	X-RAY DIFFRACTION	2.7
2J3N	X-RAY DIFFRACTION	2.8
2ZZ0	X-RAY DIFFRACTION	2.8
9UIN	ELECTRON MICROSCOPY	3.03
2ZZB	X-RAY DIFFRACTION	3.2
7X1R	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

No AlphaFold model available for Q16881 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Catalytic / active sites (1): 622 (proton acceptor)

Ligand- & substrate-binding residues (18): 281–282; 311; 316; 348–354; 350; 371–372; 376–378; 376; 442–443; 465; 484; 491–493 …

Post-translational modifications (4): 1, 218, 281, 647–648

Disulfide bonds (1): 209–214

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2408550	Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-499943	Interconversion of nucleotide di- and triphosphates
R-HSA-5263617	Metabolism of ingested MeSeO2H into MeSeH
R-HSA-5336415	Uptake and function of diphtheria toxin
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes

MSigDB gene sets: 361 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, FISCHER_G1_S_CELL_CYCLE, ENK_UV_RESPONSE_KERATINOCYTE_UP, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_4NM_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PATIL_LIVER_CANCER, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_CELL_REDOX_HOMEOSTASIS, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, TCF11_01

GO Biological Process (7): mesoderm formation (GO:0001707), signal transduction (GO:0007165), cell population proliferation (GO:0008283), cell redox homeostasis (GO:0045454), response to oxidative stress (GO:0006979), gastrulation (GO:0007369), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (9): thioredoxin-disulfide reductase (NADPH) activity (GO:0004791), identical protein binding (GO:0042802), NADPH peroxidase activity (GO:0050137), FAD binding (GO:0071949), nucleotide binding (GO:0000166), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor (GO:0016668), flavin adenine dinucleotide binding (GO:0050660)

GO Cellular Component (7): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Selenoamino acid metabolism	2
Regulation of lipid metabolism by PPARalpha	1
Cellular response to chemical stress	1
Metabolism of nucleotides	1
Uptake and actions of bacterial toxins	1
Transcriptional Regulation by TP53	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	2
cytoplasm	2
intracellular membrane-bounded organelle	2
formation of primary germ layer	1
mesoderm morphogenesis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular homeostasis	1
response to stress	1
ectoderm formation	1
endoderm formation	1
mesoderm formation	1
embryonic morphogenesis	1
cellular detoxification	1
antioxidant activity	1
protein-disulfide reductase [NAD(P)H] activity	1
protein binding	1
peroxidase activity	1
flavin adenine dinucleotide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
nucleotide binding	1
anion binding	1
nucleolus	1
nuclear lumen	1
intracellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

3900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNRD1	TXN	P10599	994
TXNRD1	TXN2	Q99757	927
TXNRD1	GPX2	P18283	877
TXNRD1	GLRX	P35754	866
TXNRD1	GPX3	P22352	859
TXNRD1	SRXN1	Q9BYN0	852
TXNRD1	GPX7	Q96SL4	844
TXNRD1	GPX6	P59796	833
TXNRD1	GPX8	Q8TED1	828
TXNRD1	GPX5	O75715	822
TXNRD1	GCLC	P48506	781
TXNRD1	SELENOT	P62341	768
TXNRD1	SELENOS	Q9BQE4	766
TXNRD1	NQO1	P15559	762
TXNRD1	GCLM	P48507	761

IntAct

34 interactions, top by confidence:

A	B	Type	Score
CAV1	TXNRD1	psi-mi:“MI:0915”(physical association)	0.630
TXNRD1	CAV1	psi-mi:“MI:0407”(direct interaction)	0.630
CAV1	TXNRD1	psi-mi:“MI:0403”(colocalization)	0.630
PDIA6	TXNRD1	psi-mi:“MI:0914”(association)	0.560
TXNRD1	PDIA6	psi-mi:“MI:0915”(physical association)	0.560
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
CDO1	DBT	psi-mi:“MI:0914”(association)	0.530
TXNRD1	Cav1	psi-mi:“MI:0403”(colocalization)	0.430
Cav1	TXNRD1	psi-mi:“MI:0403”(colocalization)	0.430
TXNRD2	TXNRD1	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TXNRD1	DMRTC2	psi-mi:“MI:0915”(physical association)	0.370
OPA3	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
TXNRD1	trxA	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
rep	PCNT	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
RP2	QSOX1	psi-mi:“MI:0914”(association)	0.350
PDIA6	PLS1	psi-mi:“MI:0914”(association)	0.350
RP2	STOM	psi-mi:“MI:0914”(association)	0.350
PIDD1	IPO5	psi-mi:“MI:0914”(association)	0.350
SOX2	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
SWSAP1	NACA	psi-mi:“MI:2364”(proximity)	0.270
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (138): TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), NAPRT (Co-fractionation), TRIM25 (Co-fractionation), TXNRD1 (Co-fractionation), TXNRD1 (Co-fractionation), TXNRD1 (Co-fractionation), TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-MS), TXNRD1 (Affinity Capture-RNA), TXNRD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0L1JEZ9, A0A0U1LQD9, A0A142C7A5, A0A1B2CTB0, A0A2G5IC53, A0A397HQ89, A0A411PQP8, A1A653, A8NF99, B2KWH9, B2KWI1, B8NM63, D2E9W9, D4AU57, G1XSR6, G5EB76, I1R9B0, I1RN13, M2PP75, N4WYI1, O43029, O80874, O94284, O95831, P0DXV5, P0DXV6, P25415, P38997, P80324, P82861, P92947, Q0D1P2, Q0UI02, Q16881, Q2I0M6, Q2RBS5, Q2TZB2, Q4WAZ0, Q4WD48, Q75BV4

Diamond homologs: A2TIL1, B9A1H3, D0VWY5, D9J041, O04955, O15770, O34324, O62768, O89049, P00390, P06715, P0A0E4, P0A0E5, P13110, P16171, P23189, P27456, P28593, P30635, P35484, P39040, P39050, P39051, P39916, P41921, P42770, P43783, P47791, P48638, P48639, P48640, P48641, P48642, P61076, P70619, P78965, P80461, P80647, P85207, P91938

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3657 predictions. Top by Δscore:

Variant	Effect	Δscore
12:104251525:A:AG	acceptor_gain	1.0000
12:104251526:G:GG	acceptor_gain	1.0000
12:104311288:A:AG	acceptor_gain	1.0000
12:104311288:AG:A	acceptor_gain	1.0000
12:104311289:G:GA	acceptor_gain	1.0000
12:104311289:GG:G	acceptor_gain	1.0000
12:104311289:GGC:G	acceptor_gain	1.0000
12:104311289:GGCTT:G	acceptor_gain	1.0000
12:104311393:G:GT	donor_gain	1.0000
12:104311408:C:G	donor_gain	1.0000
12:104313239:TTCCA:T	acceptor_loss	1.0000
12:104313240:TCCA:T	acceptor_loss	1.0000
12:104313241:CCA:C	acceptor_loss	1.0000
12:104313242:CAG:C	acceptor_loss	1.0000
12:104313244:G:GA	acceptor_loss	1.0000
12:104313244:GGA:G	acceptor_gain	1.0000
12:104313315:GGG:G	donor_gain	1.0000
12:104313316:GGG:G	donor_gain	1.0000
12:104315769:T:A	acceptor_gain	1.0000
12:104315773:GTA:G	acceptor_loss	1.0000
12:104315774:TAG:T	acceptor_loss	1.0000
12:104315775:A:AG	acceptor_gain	1.0000
12:104315775:AGGTC:A	acceptor_loss	1.0000
12:104315776:G:GA	acceptor_gain	1.0000
12:104315776:GGT:G	acceptor_gain	1.0000
12:104315881:A:T	donor_gain	1.0000
12:104315892:GACAG:G	donor_gain	1.0000
12:104315895:AGGT:A	donor_loss	1.0000
12:104315896:GG:G	donor_loss	1.0000
12:104315897:G:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012528 (12:104333046 G>C), RS1000020450 (12:104290029 C>A), RS1000054687 (12:104216273 G>A,T), RS1000078235 (12:104299776 A>C), RS1000087019 (12:104216469 C>A,T), RS1000106768 (12:104303449 T>G), RS1000116094 (12:104241633 G>T), RS1000125236 (12:104248553 G>T), RS1000131423 (12:104333388 A>C), RS1000155064 (12:104214547 A>C), RS1000205135 (12:104253706 G>T), RS1000255707 (12:104253891 C>T), RS1000293297 (12:104302742 G>T), RS1000309998 (12:104235606 A>T), RS1000331868 (12:104223055 C>A,T)

Disease associations

OMIM: gene MIM:601112 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002671_12	Toenail selenium levels	1.000000e-06
GCST006585_2701	Blood protein levels	5.000000e-06
GCST007006_12	Logical memory (delayed recall) in normal cognition	7.000000e-07
GCST008476_12	Emphysema annual change measurement in smokers (percent low attenuation area)	8.000000e-06
GCST012100_2	Hypertrophic cardiomyopathy (sarcomere positive)	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0007626	emphysema imaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1927 (SINGLE PROTEIN), CHEMBL2096978 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 231,338 (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
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4	113,934
CHEMBL140	CURCUMIN	3	93,882
CHEMBL406050	PX-12	2	324
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL2035460	ETHASELEN	1	50

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Thioredoxin (Trx) system proteins

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
parthenolide	Inhibition	5.52	pIC50
micheliolide	Inhibition	5.21	pIC50
TrxR1 inhibitor 6a	Binding	5.1	pKd

Binding affinities (BindingDB)

7 measured of 7 human assays (7 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[[(2S)-1-[(2-ethoxy-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]prop-2-enyl 2,6-bis(trifluoromethyl)benzoate	IC50	2800 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system
2-[[1-[(2-ethoxy-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]prop-2-enyl 2,6-dichlorobenzoate	IC50	2900 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system
2-[[1-[(2-ethoxy-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]prop-2-enyl 2,6-bis(trifluoromethyl)benzoate	IC50	3200 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system
2-[[(2R)-1-[(2-ethoxy-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]prop-2-enyl 2,6-bis(trifluoromethyl)benzoate	IC50	3500 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system
2-(benzylcarbamoyl)prop-2-enyl 2,6-dichlorobenzoate	IC50	5900 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system
2-(benzylcarbamoyl)prop-2-enyl 2,6-bis(trifluoromethyl)benzoate	IC50	8600 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system
2-(butan-2-yldisulfanyl)-1H-imidazole	IC50	15400 nM	US-9018255: Esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them, and their use as inhibitors of the thioredoxin—thioredoxin reductase system

ChEMBL bioactivities

151 potent at pChembl≥5 of 199 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.96	IC50	0.11	nM	2-(2-Amino-ethylamino)-N-(7-{2-[N’-(5-nitro-furan-2-carbonyl)-hydrazino]-2-oxo-ethyl}-naphthalen-2-yl)-acetamide; compound with GENERIC INORGANIC NEUTRAL COMPONENT
9.92	IC50	0.12	nM	2-(2-Amino-ethylamino)-N-(7-{2-[N’-(5-nitro-furan-2-carbonyl)-hydrazino]-2-oxo-ethyl}-naphthalen-2-yl)-acetamide; compound with GENERIC INORGANIC NEUTRAL COMPONENT
9.07	IC50	0.854	nM	CHEMBL5858773
8.99	IC50	1.03	nM	CHEMBL6007625
8.82	IC50	1.52	nM	CHEMBL5891038
8.70	IC50	2	nM	Platinum complex
8.52	IC50	3	nM	2-Mercaptoimidazole Bis[(4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II)] Trinitrate
8.50	IC50	3.16	nM	CHEMBL5749180
8.40	Ki	4	nM	Platinum complex
8.40	IC50	4	nM	4-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.40	IC50	3.99	nM	CHEMBL5965472
8.36	IC50	4.35	nM	CHEMBL5863993
8.30	IC50	5	nM	Platinum complex
8.30	Ki	5	nM	4-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.30	IC50	5.05	nM	CHEMBL5900218
8.26	IC50	5.5	nM	CHEMBL5917158
8.22	IC50	6	nM	2-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.17	IC50	6.78	nM	CHEMBL5758824
8.16	IC50	6.9	nM	CHEMBL5965930
8.15	Ki	7	nM	2-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.15	IC50	7	nM	2-Mercaptopyrimidine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.14	IC50	7.16	nM	CHEMBL5795370
8.13	IC50	7.33	nM	CHEMBL5932372
8.12	IC50	7.6	nM	CHEMBL5908415
8.04	IC50	9.21	nM	CHEMBL4859206
8.04	IC50	9.226	nM	CHEMBL4859206
7.97	IC50	10.8	nM	CHEMBL5836958
7.96	Ki	11	nM	2-Mercaptoimidazole Bis[(4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II)] Trinitrate
7.91	IC50	12.3	nM	CHEMBL5989199
7.88	IC50	13.19	nM	CHEMBL1876217
7.88	IC50	13.21	nM	CHEMBL1876217
7.84	IC50	14.5	nM	CHEMBL5783957
7.77	Ki	17	nM	2-Mercaptopyrimidine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
7.75	IC50	18	nM	CHEMBL120147
7.75	IC50	17.89	nM	CHEMBL4849098
7.75	IC50	17.91	nM	CHEMBL4849098
7.74	IC50	18.2	nM	CHEMBL5961197
7.73	IC50	18.8	nM	CHEMBL6018328
7.69	IC50	20.3	nM	CHEMBL5759558
7.66	Ki	22	nM	4-Mercaptoethanol-(2,2’:6’,4’-chloro,2’’-terpyridine)platinum (II) Nitrate
7.60	IC50	25	nM	Platinum complex
7.60	IC50	25.3	nM	CHEMBL5739752
7.57	IC50	26.8	nM	CHEMBL5917158
7.52	IC50	30	nM	4-Mercaptoethanol-(2,2’:6’,4’-chloro,2’’-terpyridine)platinum (II) Nitrate
7.46	Ki	35	nM	Platinum complex
7.46	IC50	35	nM	4-Mercaptoethanol-(2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
7.42	IC50	38	nM	2-(2-Amino-ethylamino)-N-(7-{2-[N’-(5-nitro-furan-2-carbonyl)-hydrazino]-2-oxo-ethyl}-naphthalen-2-yl)-acetamide; compound with GENERIC INORGANIC NEUTRAL COMPONENT
7.41	IC50	39.2	nM	CHEMBL5829094
7.41	IC50	39.1	nM	CHEMBL5837604
7.37	IC50	43.18	nM	STAUROSPORINE

PubChem BioAssay actives

69 with measured affinity, of 308 total; 47 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-[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]phenol	1778246: Inhibition of TrxR1 (unknown origin) assessed as reduction in DTNB to TNB by colorimetric assay	ic50	0.0092	uM
2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenol	1778246: Inhibition of TrxR1 (unknown origin) assessed as reduction in DTNB to TNB by colorimetric assay	ic50	0.0132	uM
2-(3-benzyl-1,2,4-oxadiazol-5-yl)phenol	1778246: Inhibition of TrxR1 (unknown origin) assessed as reduction in DTNB to TNB by colorimetric assay	ic50	0.0179	uM
N’-(2-naphthalen-2-ylacetyl)-5-nitrofuran-2-carbohydrazide	255063: Inhibitory concentration against wild type human thioredoxin reductase (5 nM) pre-incubated for 10 min at 25 degree C in buffer in the presence of 200 uM NADPH	ic50	0.0180	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1778246: Inhibition of TrxR1 (unknown origin) assessed as reduction in DTNB to TNB by colorimetric assay	ic50	0.0432	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149695: Binding affinity to human TXNRD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1900	uM
(6E)-6-[(E)-3-[4-(dimethylamino)phenyl]prop-2-enylidene]cyclohex-2-en-1-one	1677566: Inhibition of TrxR in human BEL-7402/5-FU cells by colorimetric assay	ic50	0.2000	uM
(6E)-6-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enylidene]cyclohex-2-en-1-one	1677566: Inhibition of TrxR in human BEL-7402/5-FU cells by colorimetric assay	ic50	0.2000	uM
(1S,3R,6S,8S,11S,13R,16S,18R,21S,23R,26S,28S,31S,33R)-10-[[4-(dimethylamino)phenyl]tellanylmethyl]-5,15,20,25,30,35-hexakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol	213240: Inhibition of thioredoxin reductase	ic50	0.2600	uM
(1R,5S,8S,15S,18R,21S,22S)-5-methyl-7,16-dioxahexacyclo[13.6.1.01,8.04,21.09,14.018,22]docosa-9(14),11-diene-10,13,17-trione	1306725: Irreversible inhibition of thioredoxin reductase (unknown origin)	ki	0.2800	uM
8’-hydroxyspiro[2,4-dioxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaene-3,4’-naphthalene]-1’-one	213244: Inhibition of thioredoxin-1/thioredoxin reductase system	ic50	0.3500	uM
(6E)-6-[(E)-3-(4-methoxyphenyl)prop-2-enylidene]cyclohex-2-en-1-one	1677566: Inhibition of TrxR in human BEL-7402/5-FU cells by colorimetric assay	ic50	0.4000	uM
(1S,3R,6S,8R,11S,13R,16S,18R,21S,23S,26S,28R,31S,33S)-5,10,15,20,30,35-hexakis(hydroxymethyl)-25-[[(1S,3S,6S,8S,11S,13R,16S,18R,21S,23R,26S,28R,31S,33R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecahydroxy-5,15,20,25,30,35-hexakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-10-yl]methyltellanylmethyl]-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol	213241: Inhibition of thioredoxin reductase in the presence of thioredoxinand insulin	ic50	0.5000	uM
(6E)-6-[(E)-3-(4-fluorophenyl)prop-2-enylidene]cyclohex-2-en-1-one	1677566: Inhibition of TrxR in human BEL-7402/5-FU cells by colorimetric assay	ic50	0.6000	uM
(E)-N-[2-(tert-butylamino)-1-(4-methoxyphenyl)-2-oxoethyl]-4-(4-methylphenyl)-4-oxo-N-propan-2-ylbut-2-enamide	1564518: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry	ic50	0.7600	uM
5,7-dimethoxy-3-[3-[2-[(1E,4E)-3-oxo-5-pyridin-2-ylpenta-1,4-dienyl]phenoxy]propoxy]-2-(3,4,5-trimethoxyphenyl)chromen-4-one	1406040: Inhibition of TrxR in human SGC7901 cells	ic50	0.7830	uM
(E)-N-[2-(tert-butylamino)-1-(4-fluorophenyl)-2-oxoethyl]-N-cyclopropyl-4-(4-fluorophenyl)-4-oxobut-2-enamide	1564518: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry	ic50	0.8200	uM
2-[[2-(tert-butylamino)-1-(4-fluorophenyl)-2-oxoethyl]-methylamino]ethyl (E)-4-(4-fluorophenyl)-4-oxobut-2-enoate	1564518: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry	ic50	0.9600	uM
(1S,3R,6S,8S,11S,13R,16S,18R,21S,23R,26S,28S,31S,33R)-10-(butyltellanylmethyl)-5,15,20,25,30,35-hexakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol	213241: Inhibition of thioredoxin reductase in the presence of thioredoxinand insulin	ic50	1.2000	uM
(1E,4E)-1-(4-hydroxy-3-methoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one	1628168: Inhibition of thioredoxin reductase in human A549/CDDP cells by DTNB dye based microplate spectrophotometry	ic50	1.2200	uM
4-(1,3,2-dithiarsinan-2-yl)aniline	1154308: Inhibition of human TrxR activity in human HeLa cell lysate after 12 hrs by insulin reduction assay	ic50	1.4000	uM
(1S,3R,6S,8S,11S,13R,16S,18R,21S,23S,26S,28R,31S,33R)-5,10,15,20,30,35-hexakis(hydroxymethyl)-25-(phenyltellanylmethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol	213240: Inhibition of thioredoxin reductase	ic50	1.6000	uM
(1S,3R,6S,8S,11S,13R,16S,18R,21S,23S,26S,28R,31S,33R)-5,10,15,20,30,35-hexakis(hydroxymethyl)-25-[(4-methoxyphenyl)tellanylmethyl]-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol	213240: Inhibition of thioredoxin reductase	ic50	1.6000	uM
1-[(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]-2,3-dihydropyridin-6-one	1677566: Inhibition of TrxR in human BEL-7402/5-FU cells by colorimetric assay	ic50	1.8000	uM
(1E,4E)-1-(3,4,5-trimethoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one	1628168: Inhibition of thioredoxin reductase in human A549/CDDP cells by DTNB dye based microplate spectrophotometry	ic50	1.9800	uM
4,6-dinitro-2,1,3-benzothiadiazole	263781: Inhibition of human TrxR	ic50	2.0000	uM
5-methoxy-2-[2-(5-methoxy-3-oxo-1,2-benzoselenazol-2-yl)ethyl]-1,2-benzoselenazol-3-one	665478: Inhibition of TrxR in human U87MG cells after 12 hrs by insulin-reducing method	ic50	2.0000	uM
spiro[2,4-dioxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaene-3,8’-3,4-dihydro-2H-naphthalene]-1’,5’-dione	213244: Inhibition of thioredoxin-1/thioredoxin reductase system	ic50	2.1000	uM
5,8-dihydroxy-2-methylnaphthalene-1,4-dione	1503041: Inhibition of TrxR1 in human HL60 cells incubated for 24 hrs by endpoint insulin reduction assay	ic50	2.4000	uM
(E)-N-[2-(tert-butylamino)-2-oxo-1-(3,4,5-trimethoxyphenyl)ethyl]-4-(4-fluorophenyl)-N-(3-methylbutyl)-4-oxobut-2-enamide	1564518: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry	ic50	2.5100	uM
3,5,6,10,12,13-hexahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),3,5,8(16),10,12-hexaene-7,14-dione	580674: Inhibition of human thioredoxin reductase	ic50	3.0000	uM
N-[5-[3-[[4-[N’-(3-bromo-4-fluorophenyl)-N-hydroxycarbamimidoyl]-1,2,5-oxadiazol-3-yl]amino]propyl]-1,3,4-thiadiazol-2-yl]-2-(4-hydroxyphenyl)acetamide	2032189: Inhibition of TrxR1 in human HCT-116 cells incubated for 24 hrs	ec50	3.1400	uM
8’-hydroxyspiro[1,3-dioxolane-2,4’-naphthalene]-1’-one	213244: Inhibition of thioredoxin-1/thioredoxin reductase system	ic50	3.4000	uM
(E)-3-(3-nitrophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one	1199613: Inhibition of TrxR in human HeLa cells assessed as depletion of cellular thiol after 48 hrs	ic50	3.5000	uM
4-arsorosoaniline	1154308: Inhibition of human TrxR activity in human HeLa cell lysate after 12 hrs by insulin reduction assay	ic50	4.0000	uM
(1S,3R,6S,8S,11S,13R,16S,18R,21S,23S,26S,28R,31S,33R)-5,10,15,20,30,35-hexakis(hydroxymethyl)-25-[(4-hydroxyphenyl)tellanylmethyl]-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol	213241: Inhibition of thioredoxin reductase in the presence of thioredoxinand insulin	ic50	4.0000	uM
1-(2,4-dinitrophenyl)sulfanyl-2,4-dinitrobenzene	263781: Inhibition of human TrxR	ic50	4.0000	uM
(1E,4E)-1-(2,4-dimethoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one	1628167: Inhibition of thioredoxin reductase in human A549 cells by DTNB dye based microplate spectrophotometry	ic50	4.1200	uM
(1E,4E)-1-(3,4-dimethoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one	1628167: Inhibition of thioredoxin reductase in human A549 cells by DTNB dye based microplate spectrophotometry	ic50	4.1700	uM
(1’S,2’S,3’R,5’R,7’R,11’S)-2’,11’-dihydroxyspiro[2,4-dioxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaene-3,6’-4,12-dioxatetracyclo[5.4.1.01,7.03,5]dodec-9-ene]-8’-one	213244: Inhibition of thioredoxin-1/thioredoxin reductase system	ic50	4.5000	uM
(1S,3R,11R,14S)-14-(hydroxymethyl)-3-[(1S,3R,11R,14S)-14-(hydroxymethyl)-18-methyl-13,17-dioxo-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-trien-3-yl]-18-methyl-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-triene-13,17-dione	476000: Inhibition of thioredoxin reductase 1	ic50	4.6000	uM
(1E,4E)-1-(2-hydroxy-3-methoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one	1628168: Inhibition of thioredoxin reductase in human A549/CDDP cells by DTNB dye based microplate spectrophotometry	ic50	4.6400	uM
8’-(2-methylprop-2-enoxy)spiro[2,4-dioxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaene-3,4’-naphthalene]-1’-one	213244: Inhibition of thioredoxin-1/thioredoxin reductase system	ic50	4.8000	uM
2-[2-(3-oxo-1,2-benzoselenazol-2-yl)ethyl]-1,2-benzoselenazol-3-one	665478: Inhibition of TrxR in human U87MG cells after 12 hrs by insulin-reducing method	ic50	5.0000	uM
(E)-N-cyclohexyl-N-[2-(cyclohexylamino)-1-(2-methoxyphenyl)-2-oxoethyl]-4-(4-methylphenyl)-4-oxobut-2-enamide	1564518: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry	ic50	5.2800	uM
(E)-N-[2-(benzylamino)-1-(5-methylpyrimidin-2-yl)-2-oxoethyl]-N-cyclopropyl-4-(4-methylphenyl)-4-oxobut-2-enamide	1564518: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry	ic50	6.6100	uM
(3’S,10’R)-3’,10’-dihydroxyspiro[2,4-dioxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaene-3,8’-tetracyclo[10.2.1.02,11.04,9]pentadeca-4(9),6,13-triene]-5’-one	213244: Inhibition of thioredoxin-1/thioredoxin reductase system	ic50	8.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression, affects cotreatment	22
sulforaphane	affects cotreatment, decreases activity, increases activity, increases reaction, decreases expression (+3 more)	12
Tobacco Smoke Pollution	increases expression, increases reaction, affects expression, affects cotreatment	11
Sodium Selenite	increases activity, increases expression, increases reaction, affects cotreatment, increases oxidation (+4 more)	10
Cadmium Chloride	increases expression, decreases reaction, affects binding, increases reaction, increases abundance	10
Cadmium	increases abundance, increases expression, decreases reaction	8
Arsenic	affects cotreatment, affects methylation, increases expression, increases abundance	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	6
Estradiol	affects cotreatment, decreases expression, affects binding, increases reaction, increases expression	6
Hydrogen Peroxide	increases expression, decreases expression, affects reaction, decreases reaction, affects cotreatment	6
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression, increases reaction	6
methylmercuric chloride	decreases reaction, increases expression, decreases activity, decreases expression	5
Arsenic Trioxide	decreases response to substance, increases expression, affects cotreatment, affects expression, decreases activity (+2 more)	5
Acrolein	decreases reaction, increases expression, affects cotreatment, increases oxidation, decreases activity (+1 more)	5
Air Pollutants	increases expression, decreases expression, affects cotreatment, increases abundance, increases oxidation	5
Auranofin	increases activity, increases expression, increases reaction, decreases activity, increases oxidation (+1 more)	5
Cisplatin	increases reaction, decreases activity, increases expression, decreases response to substance, affects binding	5
Tetrachlorodibenzodioxin	increases expression, affects expression	5
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
cinnamaldehyde	increases expression	4
arsenite	affects binding, decreases reaction, increases activity, increases expression, increases reaction (+1 more)	4
Selenium	increases activity, increases expression, increases reaction, affects cotreatment	4
beta-Naphthoflavone	increases expression	4
bisphenol A	affects expression, affects methylation, increases expression	3
lead acetate	increases expression	3
diethyl maleate	increases expression	3
2-tert-butylhydroquinone	decreases expression, increases expression	3
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	3
monomethylarsonous acid	decreases activity, increases expression	3
(+)-JQ1 compound	affects binding, affects cotreatment, increases expression	3

ChEMBL screening assays

131 unique, capped per target: 116 binding, 15 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1023576	Binding	Activity at human recombinant TrxR1 at pH 7.4	Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum. — Antimicrob Agents Chemother
CHEMBL811689	Functional	Percent TrxR activity after exposure to 3x1 uM concentration at regular intervals of 0,24,48 hours for the period of 67 hours	Human thioredoxin reductase is efficiently inhibited by (2,2’:6’,2’ ‘-terpyridine)platinum(II) complexes. Possible implications for a novel antitumor strategy. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3N9	HCT116-TrxR1-KO	Cancer cell line	Male
CVCL_C7DS	Abcam A-549 TXNRD1 KO	Cancer cell line	Male
CVCL_C7EG	Abcam HCT 116 TXNRD1 KO	Cancer cell line	Male
CVCL_C7EU	Abcam THP-1 TXNRD1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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