SITAXENTAN

Possibly Marketed Outside US

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

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	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Antagonist 2,778		0.43 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Pulmonary arterial hypertension 35	Primary	Withdrawn	THELIN
Heart failure 103	Primary	Phase II 1,132	THELIN
Asthma 241	Primary	Phase II 1,132	THELIN

C_max

Value	Dose	Co-administered	Analyte	Population
10.2 μg/mL	100 mg 1 times / day multiple, oral	SILDENAFIL	SITAXENTAN plasma	Homo sapiens
13 μg/mL	100 mg 1 times / day steady-state, oral		SITAXENTAN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
25.2 μg × h/mL	100 mg 1 times / day multiple, oral	SILDENAFIL	SITAXENTAN plasma	Homo sapiens
40 μg × h/mL	100 mg 1 times / day steady-state, oral		SITAXENTAN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.42 h	100 mg 1 times / day multiple, oral	SILDENAFIL	SITAXENTAN plasma	Homo sapiens
7 h	100 mg 1 times / day steady-state, oral		SITAXENTAN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.5%			SITAXENTAN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT	Disc. AE: Serum transaminase increased...

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AEs

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AE	Significance	Dose	Population
Serum transaminase increased	1.8% Disc. AE	100 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT

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PubMed

Show entries

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
The endothelin system in pulmonary arterial hypertension.	2004 Feb 1	14736539
Pulmonary arterial hypertension associated to connective tissue diseases.	2005	16218473