TXNRD3

Summary

TXNRD3 (thioredoxin reductase 3, HGNC:20667) is a protein-coding gene on chromosome 3q21.3, encoding Thioredoxin reductase 3 (Q86VQ6). Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities.

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 the third TrxR, which unlike the other two isozymes, contains an additional N-terminal glutaredoxin (Grx) domain, and shows highest expression in testis. The Grx domain allows this isozyme to participate in both Trx and glutathione systems. It 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. Alternatively spliced transcript variants have been found for this gene. Experimental evidence suggests the use of a non-AUG (CUG) codon as a translation initiation codon (PMID:20018845).

Source: NCBI Gene 114112 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 134 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_052883

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20667
Approved symbol	TXNRD3
Name	thioredoxin reductase 3
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	TR2, TRXR3, TGR, TR2IT1, TXNRD3NT1, TXNR3
Ensembl gene	ENSG00000197763
Ensembl biotype	protein_coding
OMIM	606235
Entrez	114112

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000383572, ENST00000518740, ENST00000523403, ENST00000524230

RefSeq mRNA: 2 — MANE Select: NM_052883 NM_001173513, NM_052883

CCDS: CCDS77810, CCDS77811

Canonical transcript exons

ENST00000524230 — 16 exons

Exon	Start	End
ENSE00001046934	126621742	126621898
ENSE00001046940	126611037	126611132
ENSE00001046942	126631764	126631879
ENSE00001046946	126633909	126634051
ENSE00001046952	126630712	126630937
ENSE00001046953	126608499	126608633
ENSE00001046954	126629379	126629471
ENSE00001046958	126615355	126615462
ENSE00001046969	126622464	126622540
ENSE00001079416	126642032	126642151
ENSE00002097014	126654748	126655124
ENSE00002100702	126607050	126607973
ENSE00002214005	126647236	126647296
ENSE00002222725	126644297	126644401
ENSE00002229380	126646111	126646220
ENSE00002307511	126643981	126644053

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 89.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5307 / max 44.3196, expressed in 1477 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44357	2.4711	1354
44356	1.0596	774

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	89.45	gold quality
left testis	UBERON:0004533	89.34	gold quality
testis	UBERON:0000473	87.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.01	gold quality
right lobe of liver	UBERON:0001114	84.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.36	gold quality
tibial nerve	UBERON:0001323	81.28	gold quality
lower esophagus mucosa	UBERON:0035834	80.31	gold quality
stromal cell of endometrium	CL:0002255	80.28	gold quality
left ovary	UBERON:0002119	80.18	gold quality
right ovary	UBERON:0002118	79.72	gold quality
muscle of leg	UBERON:0001383	78.81	gold quality
gastrocnemius	UBERON:0001388	78.79	gold quality
apex of heart	UBERON:0002098	78.45	gold quality
ovary	UBERON:0000992	78.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.07	gold quality
islet of Langerhans	UBERON:0000006	77.90	gold quality
endocervix	UBERON:0000458	77.87	gold quality
body of uterus	UBERON:0009853	77.80	gold quality
right adrenal gland cortex	UBERON:0035827	77.56	gold quality
right adrenal gland	UBERON:0001233	77.28	gold quality
ectocervix	UBERON:0012249	77.03	gold quality
left adrenal gland cortex	UBERON:0035825	76.75	gold quality
metanephros cortex	UBERON:0010533	76.60	gold quality
lower esophagus	UBERON:0013473	76.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.51	gold quality
left adrenal gland	UBERON:0001234	76.49	gold quality
left lobe of thyroid gland	UBERON:0001120	76.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.19	gold quality
right lobe of thyroid gland	UBERON:0001119	76.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT5A, STAT5B

miRNA regulators (miRDB)

48 targeting TXNRD3, 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-574-5P	100.00	66.01	989
HSA-MIR-513A-5P	100.00	69.77	2465
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-7152-3P	99.97	67.47	849
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662

Literature-anchored findings (GeneRIF, showing 4)

• This study pertains to use of non-AUG (CUG) start codon in mouse thioredoxin reductase 3 gene, and conservation of this site in other mammals. (PMID:20018845)
• A role of GPx2, TrxR2 and TrxR3 in proliferation, apoptosis and, therefore, also during cancer development. (PMID:22683372)
• Findings represent the first characterization of hTGR and provide new insights into the reaction mechanism and the regulation of monothiol Grx-containing thioredoxin glutathione reductases. (PMID:29222842)
• [Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients]. (PMID:36621786)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	txnrd3	ENSDARG00000100374
mus_musculus	Txnrd3	ENSMUSG00000000811
rattus_norvegicus	Txnrd3	ENSRNOG00000059810
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), TXNRD1 (ENSG00000198431)

Protein

Protein identifiers

Thioredoxin reductase 3 — Q86VQ6 (reviewed: Q86VQ6)

Alternative names: Thioredoxin and glutathione reductase, Thioredoxin reductase 3 intronic transcript 1, Thioredoxin reductase 3 neighbor gene, Thioredoxin reductase TR2

All UniProt accessions (3): H0YBI6, H0YBQ0, Q86VQ6

UniProt curated annotations — full annotation on UniProt →

Function. Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Nucleus. Microsome. Endoplasmic reticulum.

Cofactor. Binds 1 FAD per subunit.

Domain organisation. The N-terminal glutaredoxin domain does not contain the C-X-X-C redox-active motif normally found in glutaredoxins but activity may be mediated through a single cysteine. The C-terminal Cys-Sec motif of one subunit of the homodimer may transfer electrons from the thiol-disulfide center to the glutaredoxin domain of the other subunit.

Miscellaneous. The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity.

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

RefSeq proteins (2): NP_001166984, NP_443115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002109	Glutaredoxin	Domain
IPR004099	Pyr_nucl-diS_OxRdtase_dimer	Domain
IPR006338	Thioredoxin/glutathione_Rdtase	Family
IPR011899	Glutaredoxin_euk/vir	Domain
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), 1 shown:

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

UniProt features (26 total): modified residue 5, helix 5, strand 4, sequence conflict 3, chain 1, domain 1, disulfide bond 1, cross-link 1, region of interest 1, turn 1, active site 1, binding site 1, non-standard amino acid 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3H8Q	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

No AlphaFold model available for Q86VQ6 — 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): 616 (proton acceptor)

Ligand- & substrate-binding residues (1): 158–187

Post-translational modifications (6): 379, 641–642, 26, 26, 41, 42

Disulfide bonds (1): 203–208

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MALE_GAMETE_GENERATION, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_CELL_REDOX_HOMEOSTASIS, GOBP_DETOXIFICATION, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, SANSOM_APC_TARGETS_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOMF_ANTIOXIDANT_ACTIVITY, chr3q21, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE

GO Biological Process (4): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), cell redox homeostasis (GO:0045454), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (5): thioredoxin-disulfide reductase (NADPH) activity (GO:0004791), flavin adenine dinucleotide binding (GO:0050660), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor (GO:0016668)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
intracellular membrane-bounded organelle	3
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cellular homeostasis	1
cellular detoxification	1
antioxidant activity	1
protein-disulfide reductase [NAD(P)H] activity	1
nucleotide binding	1
anion binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

2757 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNRD3	TXN	P10599	928
TXNRD3	SELENOT	P62341	812
TXNRD3	GPX2	P18283	810
TXNRD3	GPX3	P22352	809
TXNRD3	SELENOK	Q9Y6D0	801
TXNRD3	SELENOF	O60613	795
TXNRD3	SEPHS2	Q99611	795
TXNRD3	GPX7	Q96SL4	790
TXNRD3	SELENOO	Q9BVL4	788
TXNRD3	SELENOH	Q8IZQ5	779
TXNRD3	GPX6	P59796	776
TXNRD3	SELENOS	Q9BQE4	768
TXNRD3	SELENON	Q9NZV5	767
TXNRD3	MSRB1	Q9NZV6	752
TXNRD3	SELENOW	P63302	741

IntAct

34 interactions, top by confidence:

A	B	Type	Score
BOLA2-SMG1P6	TXNRD3	psi-mi:“MI:0915”(physical association)	0.560
SNAP29	TXNRD3	psi-mi:“MI:0915”(physical association)	0.560
TXNRD3	CINP	psi-mi:“MI:0915”(physical association)	0.560
FHL2	TXNRD3	psi-mi:“MI:0915”(physical association)	0.560
TXNRD3	BOLA1	psi-mi:“MI:0915”(physical association)	0.560
TXNRD3	PACRGL	psi-mi:“MI:0915”(physical association)	0.560
TXNRD3	ANKRD36B	psi-mi:“MI:0915”(physical association)	0.560
TXNRD3	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
H2AC12	TXNRD3	psi-mi:“MI:0915”(physical association)	0.400
TXNRD3	ATE1	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
BAG2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
KLK5	LRP5	psi-mi:“MI:0914”(association)	0.350
TRIM63	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000
TRIM55	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000
CINP	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000
FHL2	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000
BOLA1	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000
PACRGL	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000
CTNNA3	TXNRD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): TXNRD3 (Affinity Capture-RNA), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), TXNRD3 (Two-hybrid), HIST1H2AH (Proximity Label-MS), TXNRD3 (Affinity Capture-MS), TXNRD3 (Affinity Capture-MS), TXNRD3 (Affinity Capture-MS), TXNRD3 (Affinity Capture-MS)

ESM2 similar proteins: A2TIL1, B9A1H3, C3K4W1, F4JLP5, O22229, O62768, O89049, P00390, P13110, P27456, P28593, P30635, P39050, P39051, P41921, P42770, P47791, P48640, P48641, P48642, P70619, P78965, P80461, P91938, Q16881, Q25861, Q41219, Q43154, Q48KI8, Q5NVA2, Q6BPI1, Q6FRV2, Q6HA23, Q70G58, Q74ZK4, Q84PW3, Q86VQ6, Q873E8, Q8S3R2, Q8T137

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	116
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2563 predictions. Top by Δscore:

Variant	Effect	Δscore
3:126607974:C:CC	acceptor_gain	1.0000
3:126607974:CT:C	acceptor_loss	1.0000
3:126607975:T:A	acceptor_loss	1.0000
3:126608486:T:TA	donor_gain	1.0000
3:126608493:TCCTA:T	donor_loss	1.0000
3:126608494:CCTA:C	donor_loss	1.0000
3:126608495:CTAC:C	donor_loss	1.0000
3:126608497:ACC:A	donor_loss	1.0000
3:126608498:C:A	donor_loss	1.0000
3:126608500:T:TA	donor_gain	1.0000
3:126608540:G:C	donor_gain	1.0000
3:126608633:CC:C	acceptor_loss	1.0000
3:126608633:CCTT:C	acceptor_gain	1.0000
3:126608636:T:TC	acceptor_gain	1.0000
3:126608639:A:AC	acceptor_gain	1.0000
3:126608639:A:C	acceptor_gain	1.0000
3:126608642:C:CT	acceptor_gain	1.0000
3:126608643:A:T	acceptor_gain	1.0000
3:126611035:A:AC	donor_gain	1.0000
3:126611036:C:CC	donor_gain	1.0000
3:126615353:A:AC	donor_gain	1.0000
3:126615354:C:CC	donor_gain	1.0000
3:126615354:CTT:C	donor_gain	1.0000
3:126615356:T:TA	donor_gain	1.0000
3:126615380:T:TA	donor_gain	1.0000
3:126615458:TCACA:T	acceptor_gain	1.0000
3:126615459:CACA:C	acceptor_gain	1.0000
3:126615459:CACAC:C	acceptor_gain	1.0000
3:126615461:CA:C	acceptor_gain	1.0000
3:126615463:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000140189 (3:126641505 C>T), RS1000214750 (3:126634423 A>C,G), RS1000230080 (3:126626979 T>C), RS1000404690 (3:126619893 T>C), RS1000488037 (3:126649192 T>C), RS1000512032 (3:126612588 T>C), RS1000590526 (3:126655792 C>A), RS1000653903 (3:126635164 A>G), RS1000662377 (3:126642286 A>C,G), RS1000847059 (3:126615328 T>A), RS1000897326 (3:126608752 T>A,C), RS1000924591 (3:126628741 T>C), RS1000975866 (3:126613296 G>A), RS1000985067 (3:126646890 T>A,C), RS1000994973 (3:126622012 C>T)

Disease associations

OMIM: gene MIM:606235 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003262_628	Post bronchodilator FEV1	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096978 (PROTEIN FAMILY), CHEMBL3793 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 117,080 (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
CHEMBL140	CURCUMIN	3	93,882
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL2035460	ETHASELEN	1	50

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

ChEMBL bioactivities

70 potent at pChembl≥5 of 103 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
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
8.40	Ki	4	nM	Platinum complex
8.40	IC50	4	nM	4-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.30	IC50	5	nM	Platinum complex
8.30	Ki	5	nM	4-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
8.22	IC50	6	nM	2-Mercaptopyridine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
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
7.96	Ki	11	nM	2-Mercaptoimidazole Bis[(4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II)] Trinitrate
7.77	Ki	17	nM	2-Mercaptopyrimidine (4’-chloro-2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
7.75	IC50	18	nM	CHEMBL120147
7.66	Ki	22	nM	4-Mercaptoethanol-(2,2’:6’,4’-chloro,2’’-terpyridine)platinum (II) Nitrate
7.60	IC50	25	nM	Platinum complex
7.52	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
6.89	IC50	130	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
6.86	Ki	139	nM	Platinum complex
6.84	IC50	145	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
6.70	IC50	200	nM	Platinum complex
6.67	IC50	215	nM	CHEMBL120147
6.58	IC50	260	nM	CHEMBL217200
6.56	Ki	275	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
6.55	Ki	280	nM	CHEMBL3814977
6.47	Ki	337	nM	Platinum complex
6.46	Ki	348	nM	4-Mercaptoethanol-(2,2’:6’,2’’-terpyridine)platinum (II) Nitrate
6.46	IC50	350	nM	CHEMBL88230
6.30	IC50	500	nM	CHEMBL412348
5.92	IC50	1200	nM	CHEMBL413290
5.91	IC50	1220	nM	CHEMBL4451948
5.85	IC50	1400	nM	CHEMBL3290761
5.83	IC50	1490	nM	CHEMBL4451948
5.80	IC50	1600	nM	CHEMBL440625
5.80	IC50	1600	nM	CHEMBL385299
5.70	IC50	2000	nM	CHEMBL2035489
5.70	IC50	2000	nM	CHEMBL206140
5.70	IC50	1980	nM	CHEMBL4475597
5.68	IC50	2100	nM	CHEMBL89232
5.63	IC50	2360	nM	CHEMBL4475597
5.62	IC50	2400	nM	CHEMBL412348
5.53	IC50	2950	nM	CHEMBL4451948
5.52	IC50	3000	nM	CORULEOELLAGIC ACID
5.51	IC50	3060	nM	CHEMBL4475597
5.47	IC50	3400	nM	CHEMBL217200
5.47	IC50	3400	nM	CHEMBL91078
5.46	IC50	3500	nM	CHEMBL32856

PubChem BioAssay actives

44 with measured affinity, of 211 total; 27 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
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
(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
(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
(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
(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
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
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
(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
(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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
belinostat	decreases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Catechin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Fluorouracil	affects reaction, decreases expression	1
Malathion	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

87 unique, capped per target: 72 binding, 15 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1694678	Binding	Inhibition of human thioredoxin reductase	Compounds structurally related to ellagic acid show improved antiplasmodial activity. — 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

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3KG	Abcam HEK293T TXNRD3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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