Ethaselen

Ethaselen (BBSKE) is an orally active, selective thioredoxin reductase (TrxR) inhibitor with IC₅₀s of 0.5 and 0.35 μM for the wild-type human TrxR1 and rat TrxR1, respectively. Ethaselen specifically binds to the unique selenocysteine-cysteine redox pair in the C-terminal active site of mammalian TrxR1. Ethaselen, an organoselenium compound, is a potent antitumor candidate that exerts potent inhibition on non-small cell lung cancer (NSCLC) by targeting TrxR^[1][2]. IC50 & Target:TrxR^[1] In Vitro: Ethaselen (2.5-10 μM; 12, 24 hours) suppresses A549 cell viability in a both concentration- and time-dependent manner. H1666, which has considerably lower TrxR1 expression level, is less susceptible to 24 h treatment with Ethaselen^[1].
Ethaselen inhibits the intracellular TrxR1 activity in a concentration- and time-dependent manner, with IC₅₀ values of 4.2 and 2 μM for 12- and 24-h treatments, respectively^[1].
Ethaselen (2.5-10 μM; 12, 24 hours) has no effect on the protein amounts of TrxR1 and Trx. The mRNA level of TrxR1 does not show significant alteration in Ethaselen-treated A549 cells^[1].
Ethaselen (2.5-50 μM; 1-24 hours) causes intracellular Trx oxidation in A549 cells^[1].
Ethaselen (5-10 μM; 12, 24 hours) causes a clear concentration-dependent increase in ROS levels in A549 cells^[1].
The inhibition constants for Ethaselen binding to free enzyme (K_i) and the enzyme-substrate complex (K_is) were determined to be 0.022 and 0.087 μM, respectively. Ethaselen also inhibits mammalian TrxR1 in a time-dependent manner possibly by forming a covalent Se-S bond with Cys497 of Trx^[1].
In Vivo: Ethaselen (BBSKE; 36-108 mg/kg/day; PO; for 10 days) shows increased inhibition of tumor growth in a dose-independent manner^[2].