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Sitaxentan sodium (formerly IPI-1040; TBC-11251; IPI 1040; TBC11251; Thelin), the sodium salt of Sitaxentan, is a selective and orally bioavailable endothelin A receptor (ETA) antagonist with anti-hypertensive activity. It suppresses ETA with IC50 and Ki of 1.4 nM and 0.43 nM, respectively. For the treatment of pulmonary arterial hypertension (PAH), sitaxentani is an authorized drug.
Physicochemical Properties
| Molecular Formula | C18H14CLN2NAO6S2 | |
| Molecular Weight | 476.89 | |
| Exact Mass | 475.988 | |
| Elemental Analysis | C, 45.34; H, 2.96; Cl, 7.43; N, 5.87; Na, 4.82; O, 20.13; S, 13.45 | |
| CAS # | 210421-74-2 | |
| Related CAS # | Sitaxsentan; 184036-34-8 | |
| PubChem CID | 11477084 | |
| Appearance | Light yellow to yellow solid powder | |
| LogP | 4.9 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 9 | |
| Rotatable Bond Count | 6 | |
| Heavy Atom Count | 30 | |
| Complexity | 726 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | ClC1C(C([H])([H])[H])=NOC=1[N-]S(C1C([H])=C([H])SC=1C(C([H])([H])C1=C([H])C2=C(C([H])=C1C([H])([H])[H])OC([H])([H])O2)=O)(=O)=O.[Na+] |
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| InChi Key | MDTNUYUCUYPIHE-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C18H14ClN2O6S2.Na/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18;/h3-5,7H,6,8H2,1-2H3;/q-1;+1 | |
| Chemical Name | sodium;(4-chloro-3-methyl-1,2-oxazol-5-yl)-[2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophen-3-yl]sulfonylazanide | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
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| Enzyme Assay | Binding studies are conducted using 2 mg/tube (ETA) or 0.75 mg/tube (ETB) membrane in a 30 mM HEPES buffer, pH 7.4, with 150 mM NaCl, 5 mM MgCl2, and 0.05% bacitracin. A final concentration of 0.25% DMSO is obtained by dissolving sitaxentan sodium in DMSO and diluting it with the assay buffer. In a final volume of 200 μL containing 4 pM [125I]ET-1 (1.6 nCi), competitive inhibition experiments are carried out in triplicate. In the presence of 100 nM ET-1, nonspecific binding is found. Samples are incubated for 16 hours−18 hours at 24 °C. After adding one milliliter of PBS, the experiment is centrifuged at 2000 g for 25 minutes at 4 °C. On a Genesys gamma counter, the membrane-bound radioactivity is counted after the supernatant has been decanted. | |
| Cell Assay | Transfected COS or TE 671 In six-well plates, seven cells are grown to confluence. Two milliliters of inositol-free RPMI-164 (IF-RPMI) media, containing two milliliters of [3H]myoinositol and ten percent inositol-free FCS, are added to each well's media sixteen hours before use. The wells are then incubated at 37 °C with 6% CO2. The cells undergo two PBS washes after the medium is aspirated. One milliliter 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 is used to preincubate cells for ten minutes before adding 100 μM of ET-1 at various concentrations. After that, the cells are incubated for a further forty-five minutes. The accumulated inositol phosphates are extracted using ice-cold methanol after the buffer is thrown away. After solubilizing the cells in 0.1 M NaOH, the total protein content of each well is determined using the BCA assay. | |
| Animal Protocol |
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| References |
[1]. Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes. Can J Physiol Pharmacol. 2010 Jun;88. [2]. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ET(A) receptor antagonist. Pulm Pharmacol Ther. 2000;13(2):87-97. [3]. Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1118-23. Epub 2010 Aug 6. |
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| Additional Infomation |
Drug Indication Treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and in pulmonary hypertension associated with connective tissue disease. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 33.33 mg/mL (69.89 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0969 mL | 10.4846 mL | 20.9692 mL | |
| 5 mM | 0.4194 mL | 2.0969 mL | 4.1938 mL | |
| 10 mM | 0.2097 mL | 1.0485 mL | 2.0969 mL |