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

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
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http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000679/WC500037902.pdf	Primary	Withdrawn	THELIN Approved Use Treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class III, to improve exercise capacity.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
Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.	1997 May 23	9171878
Emerging medical therapies for pulmonary arterial hypertension.	2002 Nov-Dec	12525997
High glucose-induced, endothelin-dependent fibronectin synthesis is mediated via NF-kappa B and AP-1.	2003 Feb	12388107
Pulmonary arterial hypertension associated to connective tissue diseases.	2005	16218473
Therapeutic targets in systemic sclerosis.	2007	17767744
Clinical trials and basic research: defining mechanisms and improving treatment in connective tissue disease.	2007	17767739
Sitaxentan: in pulmonary arterial hypertension.	2007	17385944
Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan.	2007 Jan	17234519
[Treatment of pulmonary arterial hypertension by endothelin receptor antagonists in 2008].	2008 Apr	18243424
Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?	2008 Aug	18562303
The management of pulmonary hypertension in children.	2008 Jul	18381346
Sitaxentan: new drug. Pulmonary hypertension: better to continue to use bosentan.	2008 Jun	18630348
[Systemic sclerosis].	2008 May	18552072
[Specific drugs for the treatment of pulmonary arterial hypertension - current status].	2008 Oct	18814092
Pulmonary arterial hypertension: on the way to a manageable disease.	2008 Sep	18729002
Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model.	2009	19715380
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient.	2009	19688101
Successful treatment of systemic-sclerosis-related digital ulcers with a selective endothelin type A receptor antagonist (sitaxentan).	2009	19590168
Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis.	2009	19558194
[Endothelin receptor antagonists - their role in pulmonary medicine].	2009 Dec	20032843
Small-molecule endothelin receptor antagonists: a review of patenting activity across therapeutic areas.	2009 Jun	19517317
Severe hepatitis associated with sitaxentan and response to glucocorticoid therapy.	2009 Jun	19483056
Bleeding events in pulmonary arterial hypertension.	2009 Jun	19335748
Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension.	2009 Jun	19335742
Integrated care and optimal management of pulmonary arterial hypertension.	2009 May 12	21197349
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	19863849
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
The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects.	2010 Jan	20078609
Long term combination treatment for severe idiopathic pulmonary arterial hypertension.	2010 Mar 26	21160759
The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension.	2010 May 6	20479949
Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension.	2010 Nov	20675359
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
Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan.	2010 Oct 29	19171388
Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses.	2010 Sep	20504865
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	23721565
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

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:43:04 UTC 2023` Edited by `admin` on `Sat Dec 16 17:43:04 UTC 2023`
Record UNII	J9QH779MEM
Record Status	`Validated (UNII)`
Record Version

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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