Synonym
TBC-11251; TBC11251; TBC 11251; TBC-11251 sodium salt, Thelin; Sitaxentan sodium
IUPAC/Chemical Name
N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]-3-thiophenesulfonamide, monosodium salt
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
SMILES Code
O=S(C1=C(C(CC2=C(C)C=C(OCO3)C3=C2)=O)SC=C1)([N-]C4=C(Cl)C(C)=NO4)=O.[Na+]
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS#
CAS#210421-74-2 (Sitaxentan sodium salt)
CAS#184036-34-8 (Sitaxentan free)
Biological target:
Sitaxentan is a potent nonpeptide ETA receptor antagonist (IC50 = 1.4 nM). It is selective for ETA over ETB receptors (IC50 = 9,800 nM).
In vitro activity:
The study provides insights into sitaxentan's hepatotoxicity, rationalizing its withdrawal from the market in 2010. Sitaxentan formed a reactive ortho-quinone metabolite, detected in vitro using liver microsomes and hepatocytes from various species. Human liver microsomes showed time-dependent inhibition of P450 3A4. The quinone metabolite reacted with glutathione, forming a conjugate. Computational modeling suggested that the 2-position on the phenyl ring is the likely site of glutathione conjugation.
Reference: Chem Res Toxicol. 2013 Jun 17;26(6):926-36. https://pubmed.ncbi.nlm.nih.gov/23721565/
In vivo activity:
Sitaxentan reduces neointimal lesion formation. Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries from adult, male C57Bl6 mice. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA / B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions.
Reference: Br J Pharmacol. 2015 Jun;172(11):2827-37. https://pubmed.ncbi.nlm.nih.gov/25598351/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
10.0 |
20.97 |
|
| DMSO |
15.0 |
31.45 |
|
| Ethanol |
5.0 |
10.48 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
476.88
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Burbank MG, Sharanek A, Burban A, Mialanne H, Aerts H, Guguen-Guillouzo C, Weaver RJ, Guillouzo A. From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062. PMID: 28369585.
2. Erve JC, Gauby S, Maynard JW Jr, Svensson MA, Tonn G, Quinn KP. Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry. Chem Res Toxicol. 2013 Jun 17;26(6):926-36. doi: 10.1021/tx4001144. Epub 2013 May 30. PMID: 23721565.
3. Duthie KM, Hadoke PW, Kirkby NS, Miller E, Ivy JR, McShane JF, Lim WG, Webb DJ. Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury. Br J Pharmacol. 2015 Jun;172(11):2827-37. doi: 10.1111/bph.13086. Epub 2015 Apr 23. PMID: 25598351; PMCID: PMC4439878.
4. Cross DM, Horsley E, Derzi M, Owen K, Stavros FL. An evaluation of reproductive and developmental toxicity of sitaxentan (thelin) in rats. Birth Defects Res B Dev Reprod Toxicol. 2012 Oct;95(5):327-36. doi: 10.1002/bdrb.21021. Epub 2012 Aug 13. PMID: 22890981.
In vitro protocol:
1. Burbank MG, Sharanek A, Burban A, Mialanne H, Aerts H, Guguen-Guillouzo C, Weaver RJ, Guillouzo A. From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062. PMID: 28369585.
2. Erve JC, Gauby S, Maynard JW Jr, Svensson MA, Tonn G, Quinn KP. Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry. Chem Res Toxicol. 2013 Jun 17;26(6):926-36. doi: 10.1021/tx4001144. Epub 2013 May 30. PMID: 23721565.
In vivo protocol:
1. Duthie KM, Hadoke PW, Kirkby NS, Miller E, Ivy JR, McShane JF, Lim WG, Webb DJ. Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury. Br J Pharmacol. 2015 Jun;172(11):2827-37. doi: 10.1111/bph.13086. Epub 2015 Apr 23. PMID: 25598351; PMCID: PMC4439878.
2. Cross DM, Horsley E, Derzi M, Owen K, Stavros FL. An evaluation of reproductive and developmental toxicity of sitaxentan (thelin) in rats. Birth Defects Res B Dev Reprod Toxicol. 2012 Oct;95(5):327-36. doi: 10.1002/bdrb.21021. Epub 2012 Aug 13. PMID: 22890981.
1: Dhaun N, Yuzugulen J, Kimmitt RA, Wood EG, Chariyavilaskul P, MacIntyre IM, Goddard J, Webb DJ, Corder R. Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism. J Am Heart Assoc. 2015 Mar 23;4(3):e001624. doi: 10.1161/JAHA.114.001624. PubMed PMID: 25801761; PubMed Central PMCID: PMC4392442.
2: Cross DM, Horsley E, Derzi M, Owen K, Stavros FL. An evaluation of reproductive and developmental toxicity of sitaxentan (thelin) in rats. Birth Defects Res B Dev Reprod Toxicol. 2012 Oct;95(5):327-36. doi: 10.1002/bdrb.21021. Epub 2012 Aug 13. PubMed PMID: 22890981.
3: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2010 May;32(4):247-88. doi: 10.1358/mf.2010.32.4.1507200. PubMed PMID: 20508873.
4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2010 Jan-Feb;32(1):47-86. PubMed PMID: 20383346.
5: Stavros F, Kramer WG, Wilkins MR. The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects. Br J Clin Pharmacol. 2010 Jan;69(1):23-6. doi: 10.1111/j.1365-2125.2009.03541.x. PubMed PMID: 20078609; PubMed Central PMCID: PMC2805874.
6: Agard C, Haloun A, Hamidou MA. [Pulmonary arterial hypertension related to systemic sclerosis in 2008]. J Mal Vasc. 2009 Feb;34(1):7-15. doi: 10.1016/j.jmv.2008.10.008. Epub 2008 Dec 9. Review. French. PubMed PMID: 19081217.
7: Moral MA, Tomillero A. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Mar;30(2):149-71. PubMed PMID: 18560631.
