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Details

Stereochemistry ACHIRAL
Molecular Formula C18H15ClN2O6S2
Molecular Weight 454.905
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SITAXENTAN

SMILES

CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC3=C(C)C=C4OCOC4=C3)=C1Cl

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
Molecular Formula C18H15ClN2O6S2
Molecular Weight 454.905
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2849
 0.43 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Withdrawn
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

2006
Primary
Phase II
1147
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

2006
Primary
Phase II
1147
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

2006
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.2 μg/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20078609/
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: SILDENAFIL
SILDENAFIL
 SITAXENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13 μg/mL
OTHER GOV'T
https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=10 | https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=11
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SITAXENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
25.2 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20078609/
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: SILDENAFIL
SILDENAFIL
 SITAXENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
40 μg × h/mL
OTHER GOV'T
https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=10 | https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=11
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SITAXENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.42 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20078609/
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: SILDENAFIL
SILDENAFIL
 SITAXENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7 h
OTHER GOV'T
https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=10 | https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=11
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SITAXENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.5%
OTHER GOV'T
https://www.ema.europa.eu/en/documents/scientific-discussion/thelin-epar-scientific-discussion_en.pdf#page=5 | https://www.ema.europa.eu/en/documents/product-information/thelin-epar-product-information_en.pdf#page=10 | https://pubmed.ncbi.nlm.nih.gov/17385944/
SITAXENTAN plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19335742/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/19335742/
Disc. AE: Serum transaminase increased...
AEs leading to
discontinuation/dose reduction:
Serum transaminase increased (1.8%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19335742/
AEs

AEs

AESignificanceDosePopulation
Serum transaminase increased 1.8%
Disc. AE
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19335742/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/19335742/
PubMed

PubMed

TitleDatePubMed
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
2013-11
Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry.
2013-06-17
Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management.
2010-12
Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension.
2010-11
Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan.
2010-10-29
Endothelin receptor antagonists are an effective long term treatment option in pulmonary arterial hypertension associated with congenital heart disease with or without trisomy 21.
2010-10
Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses.
2010-09
The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension.
2010-05-06
Long term combination treatment for severe idiopathic pulmonary arterial hypertension.
2010-03-26
Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?
2010-02-22
The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects.
2010-01
[Endothelin receptor antagonists - their role in pulmonary medicine].
2009-12
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.
2009-10
Small-molecule endothelin receptor antagonists: a review of patenting activity across therapeutic areas.
2009-06
Severe hepatitis associated with sitaxentan and response to glucocorticoid therapy.
2009-06
Bleeding events in pulmonary arterial hypertension.
2009-06
Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension.
2009-06
Integrated care and optimal management of pulmonary arterial hypertension.
2009-05-12
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
Successful treatment of systemic-sclerosis-related digital ulcers with a selective endothelin type A receptor antagonist (sitaxentan).
2009
Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis.
2009
[Specific drugs for the treatment of pulmonary arterial hypertension - current status].
2008-10
Pulmonary arterial hypertension: on the way to a manageable disease.
2008-09
Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?
2008-08
The management of pulmonary hypertension in children.
2008-07
Sitaxentan: new drug. Pulmonary hypertension: better to continue to use bosentan.
2008-06
[Systemic sclerosis].
2008-05
[Treatment of pulmonary arterial hypertension by endothelin receptor antagonists in 2008].
2008-04
Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan.
2007-01
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
Endothelin receptor antagonists.
2006-06
Pulmonary arterial hypertension associated to connective tissue diseases.
2005
The endothelin system in pulmonary arterial hypertension.
2004-02-01
High glucose-induced, endothelin-dependent fibronectin synthesis is mediated via NF-kappa B and AP-1.
2003-02
Emerging medical therapies for pulmonary arterial hypertension.
2003-01-15
Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.
1997-05-23
Patents

Patents

US20080076812
2

Sample Use Guides

In Vivo Use Guide
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
Substance Class Chemical
Created
by admin
on Wed Apr 02 09:29:24 GMT 2025
Edited
by admin
on Wed Apr 02 09:29:24 GMT 2025
Record UNII
J9QH779MEM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SITAXSENTAN
MI  
Preferred Name English
SITAXENTAN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
IPI-1040
Code English
sitaxentan [INN]
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
Sitaxentan [WHO-DD]
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 Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
WHO-ATC C02KX03
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
WHO-VATC QC02KX03
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
Code System Code Type Description
EPA CompTox
DTXSID0057673
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
MESH
C106276
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
NCI_THESAURUS
C73038
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
WIKIPEDIA
Sitaxentan
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
ChEMBL
CHEMBL282724
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
DRUG BANK
DB06268
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
INN
7952
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
EVMPD
SUB22917
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
DRUG CENTRAL
3548
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
CAS
184036-34-8
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
MERCK INDEX
m9962
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY Merck Index
FDA UNII
J9QH779MEM
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
IUPHAR
3950
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
PUBCHEM
216235
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
SMS_ID
100000087992
Created by admin on Wed Apr 02 09:29:24 GMT 2025 , Edited by admin on Wed Apr 02 09:29:24 GMT 2025
PRIMARY
Related Record Type Details
Structure of SITAXENTAN SODIUM
SALT/SOLVATE -> PARENT
ENDOTHELIN-1 RECEPTOR
TARGET -> INHIBITOR
Related Record Type Details
Structure of 1-KETO-2-HYDROXYSITAXENTAN
METABOLITE -> PARENT
Structure of 3-THIOPHENESULFONAMIDE, N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)-2-(2-(4,5-DIHYDROXY-2-METHYLPHENYL)ACETYL)-
METABOLITE -> PARENT
IN-VITRO
Structure of .GAMMA.-GLUTAMYL-S-(2-(2-(3-(((4-CHLORO-3-METHYL-5-ISOXAZOLYL)AMINO)SULFONYL)-2-THIENYL)-2-OXOETHYL)-5,6-DIHYDROXY-3-METHYLPHENYL)-L-CYSTEINYL-GLYCINE, L-
METABOLITE INACTIVE -> PARENT
IN-VITRO
Structure of 1,2-DIKETOSITAXENTAN
METABOLITE -> PARENT
Related Record Type Details
Structure of SITAXENTAN
ACTIVE MOIETY
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