Sitaxentan sodium | TBC-11251 | CAS#184036-34-8 | 210421-74-2 | ET(A) receptor antagonist

Sitaxentan sodium
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 317137

CAS#: 210421-74-2 (sodium salt)

Description: Sitaxentan, also known as TBC-11251 and IPI 1040, is a medication for the treatment of pulmonary arterial hypertension (PAH). It was marketed as Thelin. In 2010, Pfizer voluntarily removed sitaxentan from the market due to concerns about liver toxicity. Sitaxentan is a small molecule that blocks the action of endothelin (ET) on the endothelin-A (ETA) receptor selectively (by a factor of 6000 compared with the ETB).

Chemical Structure

Sitaxentan sodium

CAS# 210421-74-2 (sodium salt)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 317137
Name: Sitaxentan sodium
CAS#: 210421-74-2 (sodium salt)
Chemical Formula: C18H14ClN2NaO6S2
Exact Mass: 0.00
Molecular Weight: 476.880
Elemental Analysis: C, 45.34; H, 2.96; Cl, 7.43; N, 5.87; Na, 4.82; O, 20.13; S, 13.45

Price and Availability

Size	Price	Availability
50mg	USD 350	2 Weeks
100mg	USD 650
200mg	USD 950
500mg	USD 1650
1g	USD 2650
2g	USD 4650	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: TBC-11251; TBC11251; TBC 11251; TBC-11251 sodium salt, Thelin; Sitaxentan sodium

IUPAC/Chemical Name: sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide

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=C(C(SC=C1)=C1S(N([Na])C2=C(C(C)=NO2)Cl)(=O)=O)CC3=C(C)C=C(OCO4)C4=C3

Appearance: Solid powder

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)

Product Data:

Product Data

Instruction:

View handling instruction

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/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	10.0	20.97
	DMSO	15.0	31.45
	Ethanol	5.0	10.48

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.

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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.

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Sitaxentan sodium featured