TrxR1

TrxR1 (TXNRD1) is a cytosolic, FAD-containing selenoenzyme that reduces thioredoxin and supports cellular redox homeostasis, growth, and differentiation^[1]^[2]. Mechanistically, TrxR1 connects NADPH-dependent thioredoxin reduction with antioxidant defense, including ubiquinone reduction and regulation of the Nrf2-Keap1 stress-response system^[2]^[3]. In developmental models, Txnrd1 loss shows that cytoplasmic thioredoxin reductase is essential for embryogenesis in most developing tissues, supporting its value in genetic redox-biology studies^[4]. In cancer models, TXNRD1 inhibition induces oxidative stress in hepatocellular carcinoma and promotes ferroptosis in head and neck squamous cell carcinoma with NRF2 activation and poor anti-PD-1 response^[5]^[6]. Compared with mitochondrial TrxR2, cytosolic TrxR1 shows distinct substrate and metal-inhibitor specificities, including efficient reduction of both Trx1 and Trx2, which supports isoform-focused experimental design^[7]. For applications, irreversible TrxR1 inhibitors such as TRi-1 enable selective cytosolic TXNRD1 targeting, while RX1 provides a cellular probe for TrxR1 activity and inhibitor screening^[8]^[9].

References:

[1]. Fritz-Wolf K, et al. Crystal structure of the human thioredoxin reductase-thioredoxin complex. Nat Commun. 2011 Jul 12;2:383. [Content Brief]

[2]. Xia L, et al. The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. J Biol Chem. 2003 Jan 24;278(4):2141-6. [Content Brief]

[3]. Cebula M, et al. TrxR1 as a potent regulator of the Nrf2-Keap1 response system. Antioxid Redox Signal. 2015 Oct 1;23(10):823-53. [Content Brief]

[4]. Jakupoglu C, et al. Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol Cell Biol. 2005 Mar;25(5):1980-8. [Content Brief]

[5]. Lee D, et al. Induction of Oxidative Stress Through Inhibition of Thioredoxin Reductase 1 Is an Effective Therapeutic Approach for Hepatocellular Carcinoma. Hepatology. 2019 Apr;69(4):1768-1786. [Content Brief]

[6]. Hsieh MS, et al. Therapeutic targeting of thioredoxin reductase 1 causes ferroptosis while potentiating anti-PD-1 efficacy in head and neck cancer. Chem Biol Interact. 2024 May 25;395:111004. [Content Brief]

[7]. Rackham O, et al. Substrate and inhibitor specificities differ between human cytosolic and mitochondrial thioredoxin reductases: Implications for development of specific inhibitors. Free Radic Biol Med. 2011 Mar 15;50(6):689-99. [Content Brief]

[8]. Stafford WC, et al. Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy. Sci Transl Med. 2018 Feb 14;10(428):eaaf7444. [Content Brief]

[9]. Zeisel L, et al. Selective cellular probes for mammalian thioredoxin reductase TrxR1: rational design of RX1, a modular 1,2-thiaselenane redox probe. Chem. 2022 May 12;8(5):1493-1517. [Content Brief]

TrxR1 Inhibitors (3)

TrxR1 Related Products (3):

By Type:	Selective (2)

Cat. No.	Product Name	Effect	Purity

HY-106381A

Aurothiomalate tetramer sodium	Inhibitor	98.0%
Aurothiomalate tetramer sodium is the tetrameric form of Aurothiomalate sodium (HY-106381). Aurothiomalate tetramer sodium acts as an inhibitor of PKCI and TrxR1. Aurothiomalate tetramer sodium disrupts the PKCI-Par6-Rac1 signaling pathway, and also inhibits TrxR1 activity, TNFα-induced NF-κB activation, and the expression of pro-inflammatory genes. Aurothiomalate tetramer sodium blocks Kras-mediated BASC expansion and lung tumor growth, inhibits anchorage-independent growth and tumorigenicity of lung cancer cells, and suppresses neutrophil chemotaxis, phagocytosis, and leukocyte extravasation. Aurothiomalate tetramer sodium can be used in research related to rheumatoid arthritis and non-small cell lung cancer.

HY-168875

TrxR1 prodrug-1	Inhibitor
TrxR1 prodrug-1 (compound 5u) is a potent inhibitor of TrxR1. TrxR1 prodrug-1 exhibits significant antitumor efficiency in nude mice and NSCLC organoids.

HY-183544

Platinum(IV) Prodrug-1	Inhibitor
Platinum (IV) Prodrug-1 is a Pt (IV) prodrug and selective TrxR1 inhibitor. Platinum (IV) Prodrug-1 induces ferroptosis (Ferroptosis) by depleting glutathione, accumulating intracellular lipid peroxides, and inactivating Glutathione peroxidase 4. Platinum (IV) Prodrug-1 triggers endoplasmic reticulum stress and immunogenic cell death via excessive accumulation of intracellular ROS. Platinum (IV) Prodrug-1 exhibits anticancer activity against both Cisplatin (HY-17394)-sensitive and Cisplatin-resistant triple-negative breast cancer cells. Platinum (IV) Prodrug-1 can be used for the research of triple-negative breast cancer.

Name
Email *

	Sorry, but the email address you supplied was invalid.