Last update 01 Nov 2024

TrxR1

Last update 01 Nov 2024

Basic Info

Synonyms

Gene associated with retinoic and IFN-induced mortality 12 protein, Gene associated with retinoic and interferon-induced mortality 12 protein, GRIM-12

+ [11]

Introduction

Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form (PubMed:8577704). Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (Probable). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2. Enhances the transcriptional activity of the estrogen receptor ESR2 only (PubMed:15199063). Mediates cell death induced by a combination of interferon-beta and retinoic acid (PubMed:9774665). Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions.

Drugs associated with TrxR1

Ethaselen

Target

TrxR1

Mechanism

TrxR1 inhibitors

Active Org.

Peking University [+3]

Originator Org.

Peking University

Active Indication

Hematologic Neoplasms [+2]

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SIMR-1281

Target

GSR x TrxR1

Mechanism

GSR inhibitors [+1]

Active Org.

University of Sharjah

Originator Org.

University of Sharjah

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DVD-445

Target

TrxR1

Mechanism

TrxR1 inhibitors

Active Org.

University of Belgrade

Originator Org.

University of Belgrade

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with TrxR1

CTR20140581 / RecruitingPhase 1

乙烷硒啉分散片连续给药在TrxR高表达晚期恶性实体瘤病人中的安全性及药代动力学和药效学研究

[Translation] Safety, pharmacokinetics and pharmacodynamics of continuous administration of ethaselen dispersible tablets in patients with advanced malignant solid tumors with high TrxR expression

主要目的： 1.观察乙烷硒啉分散片连续给药在TrxR阳性肿瘤患者中的安全性 2. 研究乙烷硒啉分散片在肿瘤患者体内药代动力学 3. 研究乙烷硒啉在肿瘤患者中的药代/药效关系次要目的： 1. 观察乙烷硒啉在TrxR阳性肿瘤患者中的疗效。

[Translation]

Main objectives: 1. To observe the safety of continuous administration of ethaselen dispersible tablets in patients with TrxR-positive tumors 2. To study the pharmacokinetics of ethaselen dispersible tablets in tumor patients 3. To study the pharmacokinetic/pharmacodynamic relationship of ethaselen in tumor patients Secondary objectives: 1. To observe the efficacy of ethaselen in patients with TrxR-positive tumors.

Start Date29 Aug 2014

Sponsor / Collaborator

Peking University

[+1]

NCT02166242 / CompletedPhase 1IIT

Phase 1c Single Arm Study of Thioredoxin Reductase Inhibitor Ethaselen, for the Treatment of Thioredoxin Reductase High Expressed Advanced Non-small Cell Lung Cancers Who Have Received More Than Two Lines Standard Treatment.

Thioredoxin reductase plays an critical role in lung cancer patients, in vitro study showed that, ethaselen, specific inhibitor of thioredoxin reductase, could inhibit lung cancer cell growth and induce apoptosis. In China, phase 1 clinical trials of ethaselen showed that 1200 mg dose ethaselen could be well tolerated, in pre-clinical study we found that, approximately 50% non-small cell lung cancers harbored high thioredoxin reductase expression(IHC result ++ or +++), phase 1a/b of ethaselen had finished in 2008, the result showed that 1200mg ethaselen per day was safety and tolerated by Chinese malignant tumor patients.In pre-clinical research, our group found that, elevated of thioredoxin reductase activity was associated with the expression of thioredoxin reductase tested by immunohistochemistry, which means high expression of this enzyme may be a favourite predicted factor of ethaselen, the specific inhibitor of thioredoxin reductase.

Start Date01 Jun 2014

Sponsor / Collaborator

Hunan Cancer Hospital

100 Clinical Results associated with TrxR1

100 Translational Medicine associated with TrxR1

0 Patents (Medical) associated with TrxR1

1,188

Literatures (Medical) associated with TrxR1

01 Dec 2024·Molecular and Cellular Biochemistry

Melatonin antagonizes oxidative stress-induced apoptosis in retinal ganglion cells through activating the thioredoxin-1 pathway

Article

Author: Hu, Yaguang ; Gao, Shan ; Fan, Xiaojuan ; Niu, Chen ; Liang, Chen ; Cheng, Qiaochu ; Kang, Qianyan ; Wei, Ting

This study aimed to explore the role of melatonin in oxidative stress-induced injury on retinal ganglion cells and the underlying mechanisms. The immortalized RGC-5 cells were treated with H₂O₂ to induce oxidative injury. Cell viability was measured by Cell Counting Kit-8, and apoptosis was determined by flow cytometry and western blot assays. Reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels were examined to evaluate oxidative stress levels. In addition, Thioredoxin-1 (Trx1) was silenced in RGC-5 cells using small interfering RNA followed by signaling pathway examination to explore the underlying mechanisms of melatonin in alleviating oxidative injury. Melatonin pre-treatment significantly alleviated H₂O₂-induced apoptosis in RGC-5 cells. Melatonin also markedly reversed the upregulation of cleaved-caspase 3, cleaved-caspase 9, and Bax expression and downregulation of Bcl-2 expression induced by H₂O₂. Further analyses presented that melatonin significantly attenuated the increase of ROS, LDH, and MDA levels in RGC-5 cells after H₂O₂ treatment. Melatonin also abolished the downregulated expression of Superoxide dismutase type 1, Trx1, and Thioredoxin reductase 1, and the reduced activity of thioredoxin reductase in RGC-5 cells after H₂O₂ treatment. Notably, Trx1 knockdown significantly mitigated the protective effect of melatonin in alleviating H₂O₂-induced apoptosis and oxidative stress, while administration of compound C, a common inhibitor of c-Jun N-terminal kinase (JNK) signaling, partially reversed the effect of Trx1 silencing, thereby ameliorating the apoptosis and oxidative injury induced by H₂O₂ in RGC-5 cells. Melatonin could significantly alleviate oxidative stress-induced injury of retinal ganglion cells via modulating Trx1-mediated JNK signaling pathway.

01 Dec 2024·Molecular Biology Reports

Histone deacetylase inhibitor, Trichostatin A mitigates ionizing radiation induced redox imbalance by regulating NRF2/GPX4/PINK1/PARKIN signaling in mice intestine

Article

Author: Dutta, Ajaswrata ; Dahiya, Akshu ; Agrawala, Paban K ; Sharma, Suchitra

BACKGROUNDGastrointestinal-acute radiation syndrome (GI-ARS) caused by moderate to high doses of ionizing radiation exposure contribute to early death in humans. GI injury is also a common adverse effect seen in cancer patients undergoing abdominal/pelvic radiotherapy. Currently, no countermeasure agents have been approved for medical management of GI-ARS. The present study aims to evaluate the mechanism of action of Trichostatin A(TSA), a pan histone deacetylase inhibitor, against radiation-induced GI injury.METHODSTSA (150 ng/kg bw) was administered to mice 1 h and 24 h after 15 Gy abdominal irradiation. Expression of various markers of oxidative stress, mitochondrial dysfunction, and apoptosis were checked in the jejunum, and their possible regulation through the Nrf2 signaling pathway was evaluated.RESULTSTSA administered post-irradiation (15 Gy + TSA) elevated intestinal total antioxidant and glutathione levels by regulating the expression of Slc7A11 and antioxidant proteins, GCLC, GPX4, and TXNRD1. Improved mitochondrial membrane potential, ATP levels, downregulation of mitochondrial quality control proteins, (PINK1 and PARKIN), and differential regulation of the apoptotic proteins, (BAX, PUMA and BCL2) with reduced intestinal epithelial cell apoptosis in the TSA-adminstered group were observed. TSA also upregulated Nrf2 in the presence of its specific inhibitor, ML385, suggesting its involvement in regulating Nrf2 signaling during oxidative stress induced by radiation in intestine. H & E stained jejunum cross-sections revealed that TSA mitigated radiation-mediated intestinal injury in mice.CONCLUSIONSPresent findings indicate that TSA is beneficial in mitigating the damaging effects of ionizing radiation in the intestine.

01 Dec 2024·Current Opinion in Chemical Biology

Endogenous electrophiles and peroxymonocarbonate can link tyrosine phosphorylation cascades with the cytosolic TXNRD1 selenoprotein and the KEAP1/NRF2 system

Review

Author: Dagnell, Markus ; Arnér, Elias S J ; Arnér, Elias S.J.

Endogenously formed reactive molecules, such as lipid peroxides, 4-hydroxynonenal, methylglyoxal and other reactive oxygen species, can have major effects on cells. Accumulation of these molecules is counteracted by antioxidant enzymes, including the glutathione (GSH) and thioredoxin (Trx) systems, in turn regulated by the KEAP1/NRF2 system. Receptor tyrosine kinases (RTK) and their counteracting protein tyrosine phosphatases (PTP) are also modulated through redox regulation of PTP activities. The cytosolic selenoprotein thioredoxin reductase (TXNRD1) is particularly prone to attack at its easily accessible catalytic selenocysteine (Sec) residue by reactive electrophilic compounds. Therefore, we here discuss how endogenously formed electrophiles can modulate RTK/PTP signaling in a concentration- and time dependent manner by reactions either directly or indirectly linking TXNRD1 with the KEAP1/NRF2 system. Moreover, recent findings suggest that endogenous formation of peroxymonocarbonate can efficiently inhibit PTP activities and stimulate RTK signaling, seemingly bypassing PTP reduction as otherwise supported by the GSH/Trx systems.

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TrxR1

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