Sitaxsentan sodium

SKU: orb1300569

Description

Sitaxsentan sodium (TBC11251 sodium salt) is a potent and highly selective endothelin A (ETA) receptor antagonist. It is a valuable research tool for investigating the role of endothelin-1 signaling in cardiovascular diseases, pulmonary hypertension, and cancer, both in cellular and animal models.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 210421-74-2
• MW: 476.89
• Purity: 99.19%
• Formula: C₁₈H₁₄ClN₂O₆S₂·Na
• SMILES: [Na+].Cc1noc([N-]S(=O)(=O)c2ccsc2C(=O)Cc2cc3OCOc3cc2C)c1Cl
• Target: Endothelin Receptor
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:60 mg/mL (125.82 mM);Ethanol:20 mg/mL (41.94 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.19 mM)

Bioactivity

• Target IC50:
  ETA:1.4 nM
• In Vivo:
  Sitaxsentan and Bosentan, at higher concentrations, attenuate NTCP transport and inhibit human liver transport proteins, offering a potential mechanism for the increased hepatotoxicity observed in these drugs in a clinical setting. Sitaxsentan, alone or in combination with sildenafil, can completely prevent the upregulation of endothelin-1 and ETB receptor expressions. The use of Sitaxsentan alone partially restores the expression of BMPR-1A and BMPR-2. Co-administration with sildenafil further restores the expression of BMPR-1A and BMPR-2, although levels remain reduced compared to the control.
• In Vitro:
  Sitaxsentan (administered at 5 mg/kg 10 minutes before hypoxic onset) completely inhibits hypoxia-induced vasoconstriction, with no significant difference observed compared to the control group exposed to air. Oral administration of Sitaxsentan significantly attenuates the increase in mean pulmonary arterial pressure (MPAP), whereas its application in rats exposed to normal oxygen levels does not affect MPAP. Moreover, the use of Sitaxsentan alone can restrict the increase in thickness of the media (MT) caused by shunting.
• Cell Research:
  TE 671 or transfected COS 7 cells are grown to confluence in six-well plates. Sixteen hours prior to use, the media in each well is replaced with 2 mL of inositol-free RPMI-164 (IF-RPMI) media containing 10% inositol-free FCS and 2 mCi [3H]myoinositol and incubated at 37 °C in the presence of 6% CO2. The media is aspirated, and the cells are washed twice with PBS. Cells are preincubated for 10 minutes in 1 mL of lithium buffer (15 μM HEPES, pH 7.4, 145 μM NaCl, 5.4 μM KCl, 1.8 μM CaCl2, 0.8 μM MgSO4, 1.0 μM NaH2PO4, 11.2 μM glucose, 20 μM LiCl) with or without Sitaxentan sodium prior to the addition of 100 μM of ET-1 at different concentrations. Cells are then incubated for an additional 45 minutes. The buffer is discarded, and the accumulated inositol phosphates are extracted with ice cold methanol. The total cell protein in each well is measured using the BCA assay after solubilizing the cells in 0.1 M NaOH.(Only for Reference)
• Animal Research:
  Sitaxsentan is formulated in water.After an initial 2-week period of hypoxic exposure (10% O2) sitaxsentan (15 or 30 mg/kg body weight per day in the drinking water) is administered for 4 weeks during continuous exposure to hypoxia. At the conclusion of the 4 week period of hypoxia, femoral and pulmonary arterial cannulation and measurement of MPAP, MSAP, and HR are performed.

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

IPI 1040, IPI-1040, IPI1040, inhibit, Inhibitor, Endothelin Receptor, EndothelinReceptor, ET-A, TBC11251 sodium, TBC11251 sodium salt, TBC-11251, TBC 11251, TBC11251, Thelin, Sitaxsentan sodium, Sitaxentan sodium, Sitaxsentan

Compound Identifiers

PubChem CID

11477084