Ambrisentan

SKU: orb1307867

Description

Ambrisentan (BSF 208075) is a selective endothelin receptor antagonist employed in pulmonary arterial hypertension (PAH) research. It is associated with a low incidence of serum enzyme elevations and has not been linked to clinically apparent liver injury. This small molecule is utilized in both in vitro binding assays and in vivo models of pulmonary hypertension.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 177036-94-1
• MW: 378.42
• Purity: 99.86% (May vary between batches)
• Formula: C₂₂H₂₂N₂O₄
• SMILES: C([C@H](OC=1N=C(C)C=C(C)N1)C(O)=O)(OC)(C2=CC=CC=C2)C3=CC=CC=C3
• Target: Endothelin Receptor
• Solubility: Ethanol:6 mg/mL (15.86 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.29 mM);DMSO:45 mg/mL (118.92 mM)

Bioactivity

• In Vivo:
  In the Ambrisentan group, hepatic hydroxyproline content was significantly reduced (18.0 μg/g±6.1 vs. 33.9 μg/g±13.5 in the control group, P=0.014), indicating a lower level of hepatic fibrosis. Sirius red staining and α-smooth muscle actin positivity were both significantly lower in the Ambrisentan group (0.46%±0.18% vs. 1.11%±0.28%, P=0.0003; and 0.12%±0.08% vs. 0.25%±0.11%, P=0.047, respectively), suggesting reduced activation of hepatic stellate cells. RNA expression levels of procollagen-1 and TIMP-1 in the liver were significantly decreased by 60% and 45%, respectively, in the Ambrisentan group, further demonstrating its effectiveness in attenuating hepatic fibrosis. However, Ambrisentan did not significantly impact inflammation, steatosis, or endothelin-related mRNA expression in the liver. Therefore, Ambrisentan hinders the progression of hepatic fibrosis by suppressing hepatic stellate cell activation and diminishing procollagen-1 and TIMP-1 gene expression, without affecting inflammation or steatosis.
• Cell Research:
  Ambrisentan is dissolved in DMSO and stored, and then diluted with appropriate medium before use. Unless otherwise stated, for each BMEC experiment cells are randomly divided into 4 groups: (1) normoxia vehicle control (Nx-CTRL); (2) normoxia-treated; (3) hypoxia (24 h) control (Hx-CTRL) and (4) hypoxia (24 h) treated. As previously described, Nrf2 activators are added 24 h prior to any hypoxic exposures. Cell treatments are; Protandim (100 μg/mL), methazolamide (125 μg/mL, nifedipine (7 μg/mL) or Ambrisentan (40 μg/mL). In addition, some cells are treated with Nrf2 siRNA. In these experiments, siRNA is added 24 h prior to drug treatments. The rationale for 24 h hypoxia exposure for BMEC is to ensure that cells remained transfected with siRNA for the pre-treatment of drugs (24 h in normoxia) and during the 24 h hypoxia exposure. Data is collected from at least three separate cell culture preparations on three separate days (n=9).

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

BSF 208075, BSF-208075, BSF208075, Ambrisentan, inhibit, LU 208075, LU208075, LU-208075, ET-A, Endothelin Receptor, EndothelinReceptor, Inhibitor

Compound Identifiers

PubChem CID

6918493