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.

Ethaselen (2.5-10 μM; 12, 24 hours) diminishes A549 cell viability in a concentration- and time-dependent manner. H1666 cells, with lower TrxR1 expression, show reduced sensitivity to Ethaselen after 24 hours. Ethaselen selectively inhibits TrxR1 activity (IC50: 4.2 and 2 μM for 12 and 24 hours) without altering TrxR1 or Trx protein levels or TrxR1 mRNA in A549 cells. Additionally, Ethaselen (2.5-50 μM; 1-24 hours) induces Trx oxidation and increases ROS levels in A549 cells at 5-10 μM (12, 24 hours). The inhibition constants (K_i and K_is) are 0.022 and 0.087 μM, respectively, suggesting Ethaselen impedes mammalian TrxR1 possibly by forming a covalent bond with Cys497 of Trx in a time-dependent manner. A Cell Viability Assay confirms Ethaselen’s effectiveness in suppressing A549 cell viability at 2.5-10 μM over 12 and 24 hours, reinforcing its concentration and time dependency[1].

In A549 cells, using five-week-old female BALB/c nude mice as the experimental model, treatment with Ethaselen (36, 72, 108 mg/kg; PO; daily; for 10 days) resulted in increased inhibition of tumor growth, with inhibition levels increasing with the dose. The high-dose group (108 mg/kg) exhibited a greater decrease in TrxR activity levels compared to the middle-dose group (72 mg/kg) and low-dose group (36 mg/kg)[2].