SITAXENTAN

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 Search

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

Description
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
Endothelin receptor ET-A 19 Target ID: CHEMBL252 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171878/	Antagonist 2778		0.43 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Pulmonary arterial hypertension 35 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdf	Primary	Withdrawn	THELIN Approved Use Treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class III, to improve exercise capacity.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 1.16017922E12
Heart failure 103 Sources: http://adisinsight.springer.com/drugs/800007312	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 1.16017922E12
Asthma 241 Sources: http://adisinsight.springer.com/drugs/800007312	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 1.16017922E12

PubMed

Title	Date	PubMed
Endothelin receptor antagonists.	2006 Jun	16219361
The management of pulmonary hypertension in children.	2008 Jul	18381346
[Systemic sclerosis].	2008 May	18552072
[Specific drugs for the treatment of pulmonary arterial hypertension - current status].	2008 Oct	18814092
Successful treatment of systemic-sclerosis-related digital ulcers with a selective endothelin type A receptor antagonist (sitaxentan).	2009	19590168
Early intervention in pulmonary arterial hypertension associated with systemic sclerosis: an essential component of disease management.	2010 Dec	21119190
Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?	2010 Feb 22	20170553
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	20728407
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.	2013 Nov	23956101

Patents

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

Unknown

Name

Type

Language

SITAXENTAN

Official Name

English

IPI-1040

Code

English

sitaxentan [INN]

Common Name

English

SITAXSENTAN

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