U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H15ClN2O6S2
Molecular Weight 454.9073
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SITAXENTAN

SMILES

Cc1cc2c(cc1CC(=O)c3c(ccs3)S(=O)(=O)Nc4c(c(C)no4)Cl)OCO2

InChI

InChIKey=PHWXUGHIIBDVKD-UHFFFAOYSA-N
InChI=1S/C18H15ClN2O6S2/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/h3-5,7,21H,6,8H2,1-2H3

HIDE SMILES / InChI

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.43 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
THELIN

Approved Use

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.

Launch Date

1.16017922E12
Primary
THELIN

Approved Use

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.

Launch Date

1.16017922E12
Primary
THELIN

Approved Use

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.

Launch Date

1.16017922E12
PubMed

PubMed

TitleDatePubMed
Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.
1997 May 23
High glucose-induced, endothelin-dependent fibronectin synthesis is mediated via NF-kappa B and AP-1.
2003 Feb
The endothelin system in pulmonary arterial hypertension.
2004 Feb 1
Pulmonary arterial hypertension associated to connective tissue diseases.
2005
Endothelin receptor antagonists.
2006 Jun
Therapeutic targets in systemic sclerosis.
2007
Clinical trials and basic research: defining mechanisms and improving treatment in connective tissue disease.
2007
Sitaxentan: in pulmonary arterial hypertension.
2007
Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan.
2007 Jan
[Treatment of pulmonary arterial hypertension by endothelin receptor antagonists in 2008].
2008 Apr
Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?
2008 Aug
The management of pulmonary hypertension in children.
2008 Jul
Sitaxentan: new drug. Pulmonary hypertension: better to continue to use bosentan.
2008 Jun
[Systemic sclerosis].
2008 May
[Specific drugs for the treatment of pulmonary arterial hypertension - current status].
2008 Oct
Pulmonary arterial hypertension: on the way to a manageable disease.
2008 Sep
Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model.
2009
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient.
2009
[Endothelin receptor antagonists - their role in pulmonary medicine].
2009 Dec
Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension.
2009 Jun
Integrated care and optimal management of pulmonary arterial hypertension.
2009 May 12
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
Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management.
2010 Dec
Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?
2010 Feb 22
The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects.
2010 Jan
Long term combination treatment for severe idiopathic pulmonary arterial hypertension.
2010 Mar 26
The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension.
2010 May 6
Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension.
2010 Nov
Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan.
2010 Oct 29
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
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
2013 Nov
Patents

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
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.
Unknown
Name Type Language
SITAXENTAN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
IPI-1040
Code English
SITAXENTAN [WHO-DD]
Common Name English
SITAXENTAN [INN]
Common Name English
SITAXSENTAN
MI  
Common Name English
SITAXENTAN [USAN]
Common Name English
TBC-11251
Code English
N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)-2-(3,4-(METHYLENEDIOXY)-6-METHYL)PHENYLACETYL-3-THIOPHENESULFONAMIDE
Common Name English
N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)-2-((4,5-(METHYLENEDIOXY)-O-TOLY)ACETYL)-3-THIOPHENESULFONAMIDE
Common Name English
SITAXSENTAN [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 793420
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
WHO-ATC C02KX03
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
WHO-VATC QC02KX03
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
Code System Code Type Description
EPA CompTox
184036-34-8
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
MESH
C106276
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
NCI_THESAURUS
C73038
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
WIKIPEDIA
Sitaxentan
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL282724
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
DRUG BANK
DB06268
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
INN
7952
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
EVMPD
SUB22917
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
DRUG CENTRAL
3548
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
CAS
184036-34-8
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
MERCK INDEX
M9962
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY Merck Index
FDA UNII
J9QH779MEM
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
IUPHAR
3950
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY
PUBCHEM
216235
Created by admin on Fri Jun 25 21:31:40 UTC 2021 , Edited by admin on Fri Jun 25 21:31:40 UTC 2021
PRIMARY