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Thioredoxin reductase keeps cells' antioxidant defences charged; arsenic trioxide, the drug that cures most acute promyelocytic leukaemia with ATRA, inhibits it as one of its several actions.
Thioredoxin reductase 1 is a selenium-containing enzyme that recycles thioredoxin, a small protein that keeps other proteins reduced and protects against oxidative stress. Many cancers over-express it to survive their own high oxidant load. Arsenic trioxide binds the selenocysteine in the enzyme's active site and inhibits it, adding oxidative stress to its direct degradation of the PML-RARA fusion protein in acute promyelocytic leukaemia. Gold compounds such as auranofin inhibit the same enzyme and are in trials for chronic lymphocytic leukaemia and ovarian cancer.
In plain words · Thioredoxin reductase keeps cells' antioxidant defences charged; arsenic trioxide, the drug that cures most acute promyelocytic leukaemia with ATRA, inhibits it as one of its several actions.
Thioredoxin reductase keeps cells' antioxidant defences charged; arsenic trioxide, the drug that cures most acute promyelocytic leukaemia with ATRA, inhibits it as one of its several actions.
A cytosolic flavoenzyme that uses NADPH to reduce thioredoxin; it supports DNA synthesis through ribonucleotide reductase and buffers reactive oxygen species.
No product in this corpus aims at Thioredoxin reductase 1 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 1 medicine aimed at it (Arsenic trioxide) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA TXNRD1: RNA low tissue specificity; high antibody staining in 18 normal tissues; highest cancer staining prostate cancer (7 of 9 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Ovarian cancer); Open Targets associates it with 1 specific cancer type at or above 0.5 (acute promyelocytic leukemia). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas TXNRD1 tissue; Open Targets ENSG00000198431 associations
First described 1995. Earliest sequence paper UniProt cites for the protein: Gasdaska P.Y. et al, FEBS Lett, 1995, "Cloning and sequencing of a human thioredoxin reductase". Source.
A cytosolic flavoenzyme that uses NADPH to reduce thioredoxin; it supports DNA synthesis through ribonucleotide reductase and buffers reactive oxygen species.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Appendix, Bone marrow, Bronchus, Cervix, Colon, Duodenum, Fallopian tube, Heart muscle.
Medium only: breast cancer, glioma, head and neck cancer, ovarian cancer.
HPA TXNRD1 tissue · HPA TXNRD1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (antioxidant recycling); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"Thioredoxin reductase 1" OR ABSTRACT:"Thioredoxin reductase 1" OR TITLE:"TXNRD1" OR ABSTRACT:"TXNRD1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Thioredoxin reductase 1, not a curated reading list.
Shares Arsenic trioxide, Acute myeloid leukaemia.
Shares Ribonucleotide reductase (RRM1), Acute myeloid leukaemia.
Shares Arsenic trioxide, Acute myeloid leukaemia.
Shares Arsenic trioxide, Acute myeloid leukaemia.
Shares Arsenic trioxide, Acute myeloid leukaemia.
Shares Arsenic trioxide, Acute myeloid leukaemia.
Shares Arsenic trioxide, Acute myeloid leukaemia.
Shares Arsenic trioxide, Acute myeloid leukaemia.