Darusentan

SKU: orb1301774

Description

Darusentan (LU-135252) is a potent and selective endothelin receptor antagonist. It is used in research to study endothelin-mediated vasoconstriction in cardiovascular diseases, with applications in both in vitro assays and in vivo hypertension models.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 171714-84-4
• MW: 410.43
• Purity: 98.72% (May vary between batches)
• Formula: C₂₂H₂₂N₂O₆
• SMILES: COc1cc(OC)nc(O[C@H](C(O)=O)C(OC)(c2ccccc2)c2ccccc2)n1
• Target: Endothelin Receptor
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (9.75 mM);H2O:Insoluble;DMSO:125 mg/mL (304.56 mM)

Bioactivity

• In Vitro:
  Darusentan inhibits endothelin-induced signaling related to pro-contractile activity and is a potent inhibitor of vasoconstriction in large and small arteries.
• Cell Research:
  Briefly, isolated rat aortic smooth muscle cells were incubated overnight in complete media in a 96-well microplate at a density of 50 000 cells/well. The next day, cells were starved for 24 h in 0% serum conditions. Following starvation, medium was removed and cells were dosed with 20 μL of increasing concentrations of darusentan (0, 0.001, 0.01, 0.1, 1, and 10 μmol/L) made in stimulation buffer containing 50 mmol/L LiCl. Cells were incubated at 37 °C, 5% CO2 for 30 min before the addition of 20 μL of ET-1 in dose-response fashion. Cells were incubated in the presence or absence of darusentan and ET-1 at 37 °C, 5% CO2 for 60 min. Following this incubation, cells were lysed using 20 μL of 2.5% lysis solution for 30 min and lysates were transferred to a 96-well microplate pre-coated with goat anti-mouse IgG. After transfer into the ELISA plate, kit-supplied IP1-horseradish peroxidase (HRP) conjugate and anti-IP1 mAb were added to the lysates. Assays were incubated for 3 h at room temperature on a platform shaker. Assay plates were then washed 6 times with 1× ELISA wash solution (250 μL/well) before the addition of HRP substrate TMB (3, 3', 5, 5'-tetramethylbenzidine). After 20 min, the reaction was stopped and the optical density (OD) was measured at 450 nm with a correction of 620 nm. Measurements were performed in triplicate.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Darusentan, aortic, inhibit, muscle, Lu135252, Lu-135252, Lu 135252, Inhibitor, Endothelin Receptor, endothelin, Endothelin A receptor, EndothelinReceptor, ET-A, rat, receptor, RAVSMs, smooth, vascular

Compound Identifiers

PubChem CID

177236