Selenoenzymes

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Selenoenzymes

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Selenoenzymes are a family of catalytic proteins that contain at least one selenocysteine (Se-Cys) amino acid residue. In humans several selenoenzymes have been identified, including glutathione peroxidases (GPX), thioredoxin reductases (TrxR/TXNRD) and iodothyronine deiodinases (DIO).

Enzymes

glutathione peroxidase 4 Show summary »« Hide summary

Target Id

3239

Nomenclature

glutathione peroxidase 4

Genes

GPX4 (Hs), Gpx4 (Mm), Gpx4 (Rn)

Ensembl ID

ENSG00000167468 (Hs), ENSMUSG00000075706 (Mm), ENSRNOG00000013604 (Rn)

UniProtKB AC

P36969 (Hs), O35560 (Mm), GPX4_RAT (Rn)

Inhibitors

GPX4 inhibitor C18 pIC₅₀ 6.9 [1]

ML162 pIC₅₀ 5.3 [1]

Comment

Glutathione peroxidase 4 is an antioxidant enzyme that is involved in the regulation of ferroptosis. Inhibition of GPX4 is being invesitgated as a mechanism to activate ferroptosis and induce cell death in difficult to treat tumours [2-5].

References

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1. Chen T, Leng J, Tan J, Zhao Y, Xie S, Zhao S, Yan X, Zhu L, Luo J, Kong L et al.. (2023) Discovery of Novel Potent Covalent Glutathione Peroxidase 4 Inhibitors as Highly Selective Ferroptosis Inducers for the Treatment of Triple-Negative Breast Cancer. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.3c00967 [PMID:37452764]

2. Conrad M, Angeli JP, Vandenabeele P, Stockwell BR. (2016) Regulated necrosis: disease relevance and therapeutic opportunities. Nat Rev Drug Discov, 15 (5): 348-66. [PMID:26775689]

3. Forcina GC, Dixon SJ. (2019) GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis. Proteomics, 19 (18): e1800311. [PMID:30888116]

4. Lee J, Roh JL. (2023) Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience. Cancer Lett, 559: 216119. [PMID:36893895]

5. Seibt TM, Proneth B, Conrad M. (2019) Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med, 133: 144-152. [PMID:30219704]

How to cite this family page

Database page citation:

Selenoenzymes. Accessed on 28/09/2023. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1083.

Concise Guide to PHARMACOLOGY citation:

Alexander SP, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL et al. (2021) THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. Br J Pharmacol. 178 Suppl 1:S313-S411.