TrxR

Ethaselen (BBSKE) is an orally active and selective thioredoxin reductase 1 (TrxR) inhibitor with anticancer activity that directly inhibits TrxR1 activity and is commonly used in combination with oxaliplatin to inhibit tumor growth.Ethaselen induces apoptosis in cancer cells and inhibits the proliferation of colorectal cancer cells.

Auranofin (SKF-39162) is an antirheumatic agent, is used to treat rheumatoid arthritis, improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.

Sodium aurothiomalate is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Aurothiomalate sodium (Miochrysin) is a potent and selective inhibitor of oncogenic PKC-ι signaling. Aurothiomalate sodium is a potent thioredoxin reductase (TrxR) inhibitor. Aurothiomalate sodium exhibits potent anti-tumor activity.

Thioredoxin reductase (TrxR) is a biochemical reagent utilized as either a biological material or an organic compound in life sciences research.

TrxR-IN-7 (14f) is a potent inhibitor of thioredoxin reductase (TrxR), with an IC50 value of 3.5 µM. It exhibits antiproliferative activity and can induce apoptosis and the production of reactive oxygen species (ROS).

TrxR/EGFR-IN-1 (Compound L1Au2) is a TrxR/EGFR inhibitor with activity against both gefitinib-sensitive and -resistant lung cancer, effectively suppressing tumor proliferation and promoting apoptosis. It enhances GPX4 degradation through autophagosome-lysosome and proteasome pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it applicable for studies on gefitinib-resistant lung cancer.

TrxR-IN-8 (Compound 6f) is a selective inhibitor of TrxR with an IC50 of 10.2 μM. It induces apoptosis through oxidative stress by stimulating the production of reactive oxygen species, reducing intracellular thiols, and lowering the glutathione/glutathione disulfide ratio. TrxR-IN-8 exhibits significant cytotoxicity against non-small cell lung cancer (NSCLC) cells.

TrxR-IN-6 (compound 1d) is an inhibitor of TrxR that can induce the accumulation of reactive oxygen species (ROS) and possesses anticancer properties. This compound can further lead to the collapse of the redox system, inducing mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. Ultimately, it triggers oxidative stress and induces apoptosis.

TrxR-IN-9 is an inhibitor of thioredoxin reductase (TrxR) with an IC50 of 0.26 μM. It disrupts cellular redox balance and can induce S-phase cell cycle arrest, promote apoptosis, and exhibit antiproliferative activity in various cancer cells. TrxR-IN-9 exerts its effects through the synergy of nitric oxide (NO) and reactive oxygen species (ROS). This compound is applicable in research on breast cancer, gastric cancer, colorectal cancer, and liver cancer.

TrxR-IN-D9 is a novel inhibitor of thioredoxin reductase (TrxR).

TrxR-IN-3 (Compound 2c) is an effective TrxR inhibitor that exhibits strong antiproliferative activities against five human cancer cell lines, particularly breast tumor cells. It increases ROS levels, induces apoptosis by regulating apoptosis-related protein expression in breast cancer cells, and promotes autophagosome and autolysosome formation by enhancing LC3-II and Beclin-1 expression and reducing LC3-I and p62 protein expression [1].

TrxR-IN-5 (compound 4f) is an effective inhibitor of thioredoxin reductase (TrxR) with an IC₅₀ of 0.16 μM. TrxR-IN-5 increases reactive oxygen species (ROS) levels, reverses TGFβ1-induced epithelial-mesenchymal transition, and exhibits anti-proliferative and anti-metastatic effects against human breast cancer cells.

TrxR-IN-2 is a potential thioredoxin reductase (TrxR) inhibitor. TrxR-IN-2 has research value in the chemotherapy of drug-resistant hepatocellular carcinoma.

Compound 1b (TrxR-IN-4) is a potent TrxR inhibitor that activates endoplasmic reticulum stress (ERS) to induce apoptosis in HepG2 cells and mitigates CCl4-induced liver damage in vivo through TrxR expression down-regulation and reduced inflammation [1].

TrxR1-IN-B19 (TrxR1 IN B19), a TrxR1 inhibitor, selectively kills gastric cancer cells by a small molecule via targeting TrxR1 and ROS-mediated ER stress activation.

TrxR1 prodrug-1 (compound 5u) is a potent inhibitor of TrxR1, demonstrating significant antitumor activity in nude mice and NSCLC organoids.

TrxR1-IN-2 (Compound 6a) acts as a TrxR1 inhibitor that covalently bonds with the Cys475 and Sec498 sites of TrxR1. This interaction hampers TrxR1 activity, resulting in a redox homeostasis disruption and inducing apoptosis and ferroptosis.

TrxR2-IN-1 is an inhibitor of thioredoxin reductase 2 (TrxR2) with an IC50 value of 0.83 μM. It accumulates in mitochondria, disrupting their function and membrane potential, elevating reactive oxygen species (ROS) levels, and activating ASK1-mediated caspase-dependent apoptosis. TrxR2-IN-1 induces G2/M phase cell cycle arrest and inhibits cancer cell migration, making it applicable for hepatocellular carcinoma research.

Compound 5j, also known as TrxR1-IN-1, is a TrxR1 inhibitor with an IC50 of 8.8 μM. It exhibits anticancer activity, demonstrating IC50 values of 1.5 μM in MCF-7, 1.7 μM in HeLa, 2.4 μM in BGC-823, 2.8 μM in SW-480, and 2.1 μM in A549 cells. Additionally, TrxR1-IN-1 possesses antioxidant activity, effectively scavenging the DPPH radical [1].

Manumycin A is an antibiotic with anticancer activity and is a mammalian thioredoxin reductase-1 (TrxR-1) inhibitor.Manumycin A inhibits the production of IL-1β, IL-6, and IL-8 in TNF alpha-stimulated THP-1 cells and peripheral blood mononuclear cells in a dose-dependent manner, inducing apoptosis.

ZC0101 is a potent, orally active dual inhibitor of IDO1 (IC50 = 0.084 μM) and TrxR (IC50 = 7.98 μM), which effectively induces apoptosis and ROS accumulation in cancer cells [1].

DVD-445 is an effective and covalent thioredoxin reductase 1 (TrxR1) inhibitor with an IC50 of 0.60 μM. DVD-445 is a peptidomimetic compound synthesised via the Ugi reaction, featuring an electrophilic moiety and demonstrating promising anticancer potential.

Eprenetapopt (PRIMA-1Met) restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.

Photosensitizer-6 (Compound 4) is a metal ion complex that inhibits TrxR. It induces apoptosis in 4T1 cells, targeting cancer cells and eliminating tumors through chemophototherapy and immunogenic cell death under illumination. Additionally, Photosensitizer-6 can be utilized for tumor imaging.