Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H14ClN2O6S2.Na |
Molecular Weight | 476.886 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].CC1=NOC([N-]S(=O)(=O)C2=C(SC=C2)C(=O)CC3=C(C)C=C4OCOC4=C3)=C1Cl
InChI
InChIKey=MDTNUYUCUYPIHE-UHFFFAOYSA-N
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
DescriptionSources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdfCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/9171878 | http://adisinsight.springer.com/drugs/800007312 | http://www.pfizer.com/news/press-release/press-release-detail/pfizer_stops_clinical_trials_of_thelin_and_initiates_voluntary_product_withdrawal_in_the_interest_of_patient_safety
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdf
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/9171878 | http://adisinsight.springer.com/drugs/800007312 | http://www.pfizer.com/news/press-release/press-release-detail/pfizer_stops_clinical_trials_of_thelin_and_initiates_voluntary_product_withdrawal_in_the_interest_of_patient_safety
Sitaxentan (TBC11251, trade name Thelin) is a potent and selective Endothelin A receptor antagonist. Sitaxentan was under development by Encysive Pharmaceuticals (now Pfizer) for use in the treatment of pulmonary hypertension, congestive heart failure and asthma. It was launched in the major markets of the European Union (EU) under name Thelin for the treatment of pulmonary arterial hypertension. In December 2010, Pfizer discontinued clinical trials of sitaxentan worldwide and initiated voluntary product withdrawal from markets where it is approved due to life-threatening idiosyncratic risk of liver injury.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL252 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171878/ |
0.43 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | THELIN Approved UseTreatment 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. Launch Date2006 |
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Primary | THELIN Approved UseTreatment 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. Launch Date2006 |
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Primary | THELIN Approved UseTreatment 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. Launch Date2006 |
PubMed
Title | Date | PubMed |
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Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist. | 1997 May 23 |
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Endothelin receptor antagonists. | 2006 Jun |
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Therapeutic targets in systemic sclerosis. | 2007 |
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Clinical trials and basic research: defining mechanisms and improving treatment in connective tissue disease. | 2007 |
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Sitaxentan: in pulmonary arterial hypertension. | 2007 |
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Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan. | 2007 Jan |
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[Treatment of pulmonary arterial hypertension by endothelin receptor antagonists in 2008]. | 2008 Apr |
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Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? | 2008 Aug |
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The management of pulmonary hypertension in children. | 2008 Jul |
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Sitaxentan: new drug. Pulmonary hypertension: better to continue to use bosentan. | 2008 Jun |
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[Systemic sclerosis]. | 2008 May |
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[Specific drugs for the treatment of pulmonary arterial hypertension - current status]. | 2008 Oct |
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Pulmonary arterial hypertension: on the way to a manageable disease. | 2008 Sep |
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Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model. | 2009 |
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Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient. | 2009 |
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Successful treatment of systemic-sclerosis-related digital ulcers with a selective endothelin type A receptor antagonist (sitaxentan). | 2009 |
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Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis. | 2009 |
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[Endothelin receptor antagonists - their role in pulmonary medicine]. | 2009 Dec |
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Small-molecule endothelin receptor antagonists: a review of patenting activity across therapeutic areas. | 2009 Jun |
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Severe hepatitis associated with sitaxentan and response to glucocorticoid therapy. | 2009 Jun |
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Bleeding events in pulmonary arterial hypertension. | 2009 Jun |
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Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. | 2009 Jun |
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Integrated care and optimal management of pulmonary arterial hypertension. | 2009 May 12 |
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Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation. | 2009 Oct |
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Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management. | 2010 Dec |
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Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy? | 2010 Feb 22 |
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The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects. | 2010 Jan |
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Long term combination treatment for severe idiopathic pulmonary arterial hypertension. | 2010 Mar 26 |
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The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension. | 2010 May 6 |
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Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension. | 2010 Nov |
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Endothelin receptor antagonists are an effective long term treatment option in pulmonary arterial hypertension associated with congenital heart disease with or without trisomy 21. | 2010 Oct |
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Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan. | 2010 Oct 29 |
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Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses. | 2010 Sep |
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Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry. | 2013 Jun 17 |
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A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. | 2013 Nov |
Patents
Sample Use Guides
Thelin is to be taken orally as a dose of 100 mg once daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27165837
Curator's Comment: Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan or under conditions of small, interfering RNA knockdown of endothelin A receptor mRNA.
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
THELIN (AUTHORIZED: HYPERTENSION, PULMONARY)
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FDA ORPHAN DRUG |
180803
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EU-Orphan Drug |
EU/3/04/234
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m9962
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CHEMBL282724
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210421-74-2
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LL-12
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SUB22351
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C152373
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ACTIVE MOIETY
SUBSTANCE RECORD