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

Details

Stereochemistry ACHIRAL
Molecular Formula C18H15ClN2O6S2
Molecular Weight 454.905
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
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 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Withdrawn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
1132
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
1132
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
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
Endothelin receptor antagonists.
2006 Jun
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
[Endothelin receptor antagonists - their role in pulmonary medicine].
2009 Dec
Severe hepatitis associated with sitaxentan and response to glucocorticoid therapy.
2009 Jun
Integrated care and optimal management of pulmonary arterial hypertension.
2009 May 12
Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management.
2010 Dec
Long term combination treatment for severe idiopathic pulmonary arterial hypertension.
2010 Mar 26
Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension.
2010 Nov
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
Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses.
2010 Sep
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

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 Sat Dec 16 17:43:04 GMT 2023
Edited
by admin
on Sat Dec 16 17:43:04 GMT 2023
Record UNII
J9QH779MEM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SITAXENTAN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
IPI-1040
Code 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
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 Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
WHO-ATC C02KX03
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
WHO-VATC QC02KX03
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID0057673
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
MESH
C106276
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
NCI_THESAURUS
C73038
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
WIKIPEDIA
Sitaxentan
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
ChEMBL
CHEMBL282724
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
DRUG BANK
DB06268
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
INN
7952
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
EVMPD
SUB22917
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
DRUG CENTRAL
3548
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
CAS
184036-34-8
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
MERCK INDEX
m9962
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY Merck Index
FDA UNII
J9QH779MEM
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
IUPHAR
3950
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
PUBCHEM
216235
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
PRIMARY
SMS_ID
100000087992
Created by admin on Sat Dec 16 17:43:05 GMT 2023 , Edited by admin on Sat Dec 16 17:43:05 GMT 2023
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
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966