Thioredoxin Reductase (TrxR)

PX 12 inhibits hypoxia-induced HIF-1a transcriptional activity (IC50 11 nM) and proliferation of HT29 and MCF-7 tumor cells (IC50 1.9 and 0.9 uM, respectively).

Piperlongumine selectively kills cancer cells regardless of p53 status without harming normal cells. It binds to and inihbits proteins known to regulate oxidative stress, in particular, Glutathione S-transferase pi 1 (GSTP1).

CCF642 is a novel PDI-inhibiting compound with antimyeloma activity.

Manumycin A is a polyketide antibiotic that functions as an inhibitor of thioredoxin reductase 1 (TrxR-1). It exhibits anti-tumor activity by inhibiting breast cancer cell growth, potentially through LC3-mediated mechanisms. Manumycin A also downregulates pro-inflammatory cytokine release in TNF-α-stimulated human monocytes, indicating anti-inflammatory potential. Additionally, it inhibits the Ras/Raf/ERK1/2 signaling pathway and hnRNP H1 in castration-resistant prostate cancer cells, thereby suppressing exosome biogenesis and secretion.

Mito-TRFS is an innovative off-on probe designed to selectively image mitochondrial thioredoxin reductase (TrxR2) in live cells. This reagent allows for the assessment of the redox status within mitochondria, facilitating the study of oxidative stress and mitochondrial function. Mito-TRFS is particularly valuable in research focusing on cellular responses to stress and the roles of TrxR2 in various disease models.

CS47 is a reversible inhibitor of Thioredoxin reductase 1 (TrxR1). It activates stress-responsive pathways involving glutathione (GSH) and iron regulation, leading to GSH depletion, heightened heme oxygenase-1 (HO-1) expression, and intracellular iron overload, ultimately inducing ferroptosis in KRAS-independent lung cancer models. CS47 demonstrates significant anticancer activity while exhibiting low cytotoxicity towards normal lung fibroblasts, making it a valuable tool for studying cancer mechanisms and therapeutic strategies.

TrxR/EGFR-IN-1 is a potent inhibitor targeting both Thioredoxin Reductase (TrxR) and Epidermal Growth Factor Receptor (EGFR). This compound demonstrates significant anti-proliferative effects against Gefitinib-sensitive and resistant lung cancer cells, facilitating apoptosis and tumor cell death. TrxR/EGFR-IN-1 promotes GPX4 protein degradation via autophagolysosomal and proteasomal pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it a valuable tool for studying mechanisms underlying Gefitinib-resistant lung cancer.

ZC0109 is a potent dual inhibitor targeting indoleamine 2,3-dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1), exhibiting IC50 values of 50 nM and 3.0 μM, respectively. This compound is effective in inducing reactive oxygen species (ROS) accumulation and causing cell cycle arrest at the G1/S phase, ultimately leading to apoptosis in cancer cells. ZC0109 is a valuable reagent for research applications focused on cancer therapy and the modulation of immune response through IDO1 and TrxR1 inhibition.

PAO-Nap is a selective thioredoxin reductase (TrxR) inhibitor modified with a naphthalimide fluorophore linked via aminocaproic acid. This compound induces oxidative stress-mediated apoptosis in HL-60 cells, making it a valuable tool for studying apoptotic pathways and oxidative stress mechanisms in cancer research. Its unique fluorescent properties also facilitate real-time monitoring of cellular responses to TrxR inhibition.

ZC0101 is a potent dual inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) and thioredoxin reductase (TrxR), exhibiting IC50 values of 0.084 μM and 7.98 μM, respectively. This compound demonstrates significant biological activity by inducing apoptosis and promoting reactive oxygen species (ROS) accumulation in cancer cells. ZC0101 is a valuable tool for research applications aimed at understanding cancer cell metabolism and exploring therapeutic strategies targeting IDO1 and TrxR pathways.

LW-216 is a potent inhibitor of Thioredoxin Reductase 1 (TrxR1), known to induce apoptosis in cancer cells. This compound exhibits significant anti-tumor activity, making it a valuable tool for research in cancer biology and therapeutic development. Its mechanism of action and biological effects position LW-216 as an important reagent for studying redox regulation and cell death pathways in oncological contexts.

TrxR-IN-8 is a selective inhibitor of thioredoxin reductase (TrxR), exhibiting an IC50 value of 10.2 μM. This compound induces apoptosis in cancer cells through the generation of reactive oxygen species (ROS), depletion of intracellular thiols, and alteration of the glutathione/glutathione disulfide ratio. TrxR-IN-8 demonstrates considerable cytotoxic effects in non-small cell lung cancer (NSCLC) cells, making it a valuable tool in cancer research and therapeutic studies focused on oxidative stress and cell death mechanisms.

TrxR Inhibitor D9 is a potent and selective inhibitor of thioredoxin reductase (TrxR) with an EC50 of 2.8 nM. This compound effectively inhibits tumor proliferation in both in vitro and in vivo studies, making it a valuable tool for cancer research. Its ability to modulate TrxR activity supports investigations into redox biology and therapeutic strategies targeting oxidative stress in cancer cells.

TrxR-IN-6 is an inhibitor of thioredoxin reductase (TrxR), a key enzyme in maintaining the cellular redox balance. This compound induces the accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. TrxR-IN-6 effectively promotes oxidative stress, resulting in apoptosis, making it a valuable tool for cancer research and studies focusing on oxidative stress mechanisms.

Aurothioglucose is a potent inhibitor of thioredoxin reductase 1 (TrxR1), exhibiting an IC50 value of 65 nM. This compound effectively inhibits the DNA binding activity of NF-κB in vitro, highlighting its role in modulating key transcriptional pathways. Additionally, Aurothioglucose demonstrates anti-HIV and anti-rheumatic properties, making it a valuable reagent for research in infectious diseases and autoimmune disorders.

Seph-PAO is a modified para-aminooxyphenyl (PAO) compound conjugated with a sepharose fluorophore, designed to selectively detect thioredoxin reductase (TrxR). This fluorescence probe demonstrates high sensitivity and specificity, facilitating the study of TrxR activity in various biological systems. Researchers can employ Seph-PAO in investigations of oxidative stress, redox signaling, and the role of TrxR in cellular processes.

Evernic Acid is a potent inhibitor of thioredoxin reductase 1 (TrxR1), demonstrating significant antiproliferative effects on human breast cancer cells. It disrupts the NF-κB signaling pathway by preventing p65 nuclear translocation and IκBα phosphorylation, which subsequently reduces inflammatory mediators. In addition to its role as an antioxidant and neuroprotective agent, Evernic Acid protects neurons from oxidative stress and mitochondrial dysfunction. Furthermore, it inhibits key enoyl reductases in Plasmodium falciparum and downregulates quorum sensing and biofilm formation in Pseudomonas aeruginosa, showcasing its antibacterial and antifungal properties. This compound is valuable for research focused on breast cancer, neurodegenerative diseases, and microbial infections.

TrxR2-IN-1 is a selective inhibitor of thioredoxin reductase 2 (TrxR2) with an IC50 value of 0.83 μM. This compound accumulates in mitochondria, disrupts mitochondrial function and membrane potential, and enhances reactive oxygen species (ROS) production. It activates ASK1-mediated caspase-dependent apoptosis, induces G2/M cell cycle arrest, and reduces cancer cell migration. TrxR2-IN-1 is valuable for investigating hepatocellular carcinoma and related apoptotic pathways in cancer research.

TRFS-green is a selective fluorescent probe designed for the imaging of thioredoxin reductase (TrxR) in living cells. Upon activation by TrxR, TRFS-green exhibits a significant shift in its maximum absorbance from approximately 373 nm to around 440 nm. This property enables enhanced visualization of selenoprotein activity, making TRFS-green a valuable tool in cellular and biochemical research focused on redox biology and oxidative stress.

Ethaselen is a selective thioredoxin reductase (TrxR) inhibitor known for its potent inhibitory action, with IC50 values of 0.5 μM for wild-type human TrxR1 and 0.35 μM for rat TrxR1. This organoselenium compound specifically targets the unique selenocysteine-cysteine redox pair in the C-terminal active site of mammalian TrxR1. Ethaselen demonstrates significant antitumor activity, particularly against non-small cell lung cancer (NSCLC), making it a promising candidate for cancer research applications focused on apoptosis and redox regulation.

DVD-445 is a potent peptidomimetic inhibitor of thioredoxin reductase 1 (TrxR1), exhibiting an IC50 value of 0.60 μM against rat TrxR1. This compound demonstrates significant anticancer activity, making it a valuable tool for research applications focused on cancer biology and oxidative stress mechanisms. Its ability to interact covalently with TrxR1 positions DVD-445 as an important reagent for exploring therapeutic strategies targeting oxidative stress in cancer cells.

TrxR-IN-2 is a selective inhibitor of thioredoxin reductase (TrxR), a critical enzyme involved in redox regulation. This compound demonstrates significant inhibitory activity in various cancer models, particularly in drug-resistant hepatocellular carcinoma. TrxR-IN-2 is suitable for research applications focused on understanding TrxR's role in cancer biology and exploring potential therapeutic strategies against aggressive tumor types.

PMX464 is a thiol-reactive quinol that acts as an inhibitor of the thioredoxin-thioredoxin reductase (Trx/TrxR) system. This compound has been shown to inhibit NF-κB-mediated pro-inflammatory activation in human type II alveolar epithelial cells, making it a valuable tool for research focused on inflammation and oxidative stress. PMX464 is particularly useful in studies examining the role of redox signaling in various pathophysiological conditions.

TP-TRFS is a selective two-photon fluorescent probe designed to target thioredoxin reductase (TrxR). Its primary mechanism involves the detection of TrxR activity through fluorescence, making it a valuable tool for studying redox biology. This probe is particularly useful for research applications involving oxidative stress, cellular signaling, and cancer biology, enabling real-time monitoring of TrxR in live cells.

TrxR-IN-3 is a potent inhibitor of thioredoxin reductase (TrxR), exhibiting significant antiproliferative activity against various human cancer cell lines, particularly breast cancer cells. This compound enhances reactive oxygen species (ROS) levels, leading to apoptosis through the modulation of apoptosis-related proteins. Additionally, TrxR-IN-3 promotes autophagy by increasing the expression of LC3-II and Beclin-1 while reducing levels of LC3-I and p62, facilitating the formation of autophagosomes and autolysosomes. This makes TrxR-IN-3 a valuable tool for studying the mechanisms of cancer cell death and autophagy.

TrxR1-IN-1 is a selective inhibitor of thioredoxin reductase 1 (TrxR1), exhibiting an IC50 of 8.8 μM. This compound demonstrates significant anticancer activity, achieving IC50 values of 1.5 μM in MCF-7 cells, 1.7 μM in HeLa cells, 2.4 μM in BGC-823 cells, 2.8 μM in SW-480 cells, and 2.1 μM in A549 cells. Additionally, TrxR1-IN-1 possesses antioxidant properties and effectively scavenges DPPH radicals, making it a valuable tool for research in cancer biology and oxidative stress studies.

TrxR-IN-4 is a potent inhibitor of thioredoxin reductase (TrxR), demonstrating significant biological activity by inducing apoptosis in HepG2 cells via the activation of endoplasmic reticulum stress (ERS). This compound also exhibits protective effects against CCl4-induced liver damage in vivo, achieved through the down-regulation of TrxR expression and inflammatory responses. TrxR-IN-4 is a valuable tool for researching the modulation of oxidative stress and cancer therapies.

CPUL1 is a selective inhibitor of thioredoxin reductase (TrxR), demonstrating significant anti-proliferative and anti-metastatic effects in A549 lung cancer cells. It modulates epithelial-mesenchymal transition (EMT) through the induction of reactive oxygen species (ROS) and activation of ERK/JNK signaling pathways resulting from the inhibition of TrxR1 enzyme activity. CPUL1 exhibits enhanced efficacy when used in combination with α-Lipoic Acid or Dithiodipropionic acid, making it a valuable tool for cancer research and therapeutic strategies.