[CAS NO. 217798-39-5] Ethaselen
PRODUCTS SPECIFICATIONS [217798-39-5]
DESCRIPTION [217798-39-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 422.20 |
| Molecular Formula | C16H12N2O2Se2 |
| SMILES | O=C1N([Se]C2=CC=CC=C12)CCN3[Se]C4=CC=CC=C4C3=O |
Summary
Ethaselen (BBSKE) is an orally active, selective thioredoxin reductase (TrxR) inhibitor with IC 50 s 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 IC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | A549 cell |
| Concentration: | 2.5, 5, 7.5, 10 μM |
| Incubation Time: | 12, 24 hours |
| Result: | Suppressed A549 cell viability in a both concentration- and time-dependent manner. |
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Five-week-old female BALB/c nude mice with A549 cell [2] |
| Dosage: | 36, 72, 108 mg/kg |
| Administration: | PO; daily; for 10 days |
| Result: |
Showed increased inhibition of tumor growth, and the inhibition levels increased with the dose.
The TrxR activity levels of the high dose group (108 mg/kg) decreased more than the middle dose group (72 mg/kg) and low dose group (36 mg/kg). |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02166242 | Hunan Province Tumor Hospital |
Carcinoma, Non-small Cell Lung
|
June 1, 2014 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 12.5 mg/mL ( 29.61 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3685 mL | 11.8427 mL | 23.6855 mL |
| 5 mM | 0.4737 mL | 2.3685 mL | 4.7371 mL |
| 10 mM | 0.2369 mL | 1.1843 mL | 2.3685 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.25 mg/mL (2.96 mM); Clear solution
References
- [1] Lihui Wang, et al. Ethaselen: a potent mammalian thioredoxin reductase 1 inhibitor and novel organoselenium anticancer agent. Free Radic Biol Med. 2012 Mar 1;52(5):898-908.
- [2] Suo-Fu Ye, et al. Dose-biomarker-response modeling of the anticancer effect of ethaselen in a human non-small cell lung cancer xenograft mouse model. Acta Pharmacol Sin. 2017 Feb;38(2):223-232.