You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameSitaxentan
Accession NumberDB06268
TypeSmall Molecule
GroupsApproved, Investigational, Withdrawn
DescriptionSitaxentan is a medication for the treatment of pulmonary arterial hypertension (PAH). It was marketed as Thelin by Encysive Pharmaceuticals until Pfizer purchased Encysive in February 2008. In 2010, Pfizer voluntarily removed sitaxentan from the market due to concerns about liver toxicity.
Structure
Thumb
Synonyms
Sitaxsentan
External Identifiers
  • IPI-1040
  • TBC-11251
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThelinTablet100 mgOralPfizer Canada Inc2007-06-192011-04-30Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThelinTablet, film coated100 mgOralPfizer Ltd.2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer Ltd.2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer Ltd.2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer Ltd.2006-08-10Not applicableEu
ThelinTablet, film coated100 mgOralPfizer Ltd.2006-08-10Not applicableEu
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Sitaxentan sodium
210421-74-2
Thumb
  • InChI Key: MDTNUYUCUYPIHE-UHFFFAOYSA-N
  • Monoisotopic Mass: 475.9879505
  • Average Mass: 476.88
DBSALT001120
Categories
UNIIJ9QH779MEM
CAS number184036-34-8
WeightAverage: 454.905
Monoisotopic: 454.006005309
Chemical FormulaC18H15ClN2O6S2
InChI KeyPHWXUGHIIBDVKD-UHFFFAOYSA-N
InChI
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
IUPAC Name
N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-2H-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide
SMILES
CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC2=CC3=C(OCO3)C=C2C)=C1Cl
Pharmacology
IndicationInvestigated for use/treatment in pulmonary hypertension, connective tissue diseases, hypertension, and congestive heart failure.
Structured Indications Not Available
PharmacodynamicsSitaxentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Sitaxentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.
Mechanism of actionSitaxentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes pulmonary vasoconstriction. By blocking this interaction, Sitaxentan decreases pulmonary vascular resistance. Sitaxentan has a higher affinity for ET-A than ET-B.
TargetKindPharmacological actionActionsOrganismUniProt ID
Endothelin-1 receptorProteinyes
antagonist
HumanP25101 details
Endothelin B receptorProteinunknown
antagonist
HumanP24530 details
Related Articles
Absorption70-100%
Volume of distributionNot Available
Protein binding99% +
Metabolism

Hepatic (CYP2C9- and CYP3A4-mediated)

Route of eliminationRenal (50 to 60%) Fecal (40 to 50%)
Half life10 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE may increase the hypotensive activities of Sitaxentan.Experimental
AbirateroneThe metabolism of Sitaxentan can be decreased when combined with Abiraterone.Approved
AcebutololAcebutolol may increase the hypotensive activities of Sitaxentan.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Sitaxentan.Approved, Investigational
AliskirenAliskiren may increase the hypotensive activities of Sitaxentan.Approved, Investigational
AlprenololAlprenolol may increase the hypotensive activities of Sitaxentan.Approved, Withdrawn
AmbrisentanSitaxentan may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineSitaxentan may increase the hypotensive activities of Amifostine.Approved, Investigational
AmiodaroneThe metabolism of Sitaxentan can be decreased when combined with Amiodarone.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Sitaxentan.Approved
AprepitantThe metabolism of Sitaxentan can be increased when combined with Aprepitant.Approved, Investigational
AtenololAtenolol may increase the hypotensive activities of Sitaxentan.Approved
BenazeprilBenazepril may increase the hypotensive activities of Sitaxentan.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Sitaxentan.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Sitaxentan.Withdrawn
BepridilBepridil may increase the hypotensive activities of Sitaxentan.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Sitaxentan.Approved
BethanidineBethanidine may increase the hypotensive activities of Sitaxentan.Approved
BimatoprostBimatoprost may increase the hypotensive activities of Sitaxentan.Approved, Investigational
BisoprololBisoprolol may increase the hypotensive activities of Sitaxentan.Approved
BosentanBosentan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
BretyliumBretylium may increase the hypotensive activities of Sitaxentan.Approved
BrimonidineBrimonidine may increase the hypotensive activities of Sitaxentan.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Sitaxentan.Approved
BupranololBupranolol may increase the hypotensive activities of Sitaxentan.Approved
CandesartanCandesartan may increase the hypotensive activities of Sitaxentan.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Sitaxentan.Experimental
CapecitabineThe metabolism of Sitaxentan can be decreased when combined with Capecitabine.Approved, Investigational
CaptoprilCaptopril may increase the hypotensive activities of Sitaxentan.Approved
CarbamazepineThe metabolism of Sitaxentan can be increased when combined with Carbamazepine.Approved, Investigational
CaroxazoneCaroxazone may increase the hypotensive activities of Sitaxentan.Withdrawn
CarteololCarteolol may increase the hypotensive activities of Sitaxentan.Approved
CarvedilolCarvedilol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
CeliprololCeliprolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
CeritinibThe serum concentration of Sitaxentan can be increased when it is combined with Ceritinib.Approved
ChlorothiazideChlorothiazide may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Sitaxentan.Approved
CholecalciferolThe metabolism of Sitaxentan can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CilazaprilCilazapril may increase the hypotensive activities of Sitaxentan.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Sitaxentan.Approved
ClonidineClonidine may increase the hypotensive activities of Sitaxentan.Approved
ClotrimazoleThe metabolism of Sitaxentan can be decreased when combined with Clotrimazole.Approved, Vet Approved
CryptenamineCryptenamine may increase the hypotensive activities of Sitaxentan.Approved
CyclosporineThe serum concentration of Sitaxentan can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclosporineThe metabolism of Sitaxentan can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclothiazideCyclothiazide may increase the hypotensive activities of Sitaxentan.Approved
DabrafenibThe serum concentration of Sitaxentan can be decreased when it is combined with Dabrafenib.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Sitaxentan.Approved
DelavirdineThe metabolism of Sitaxentan can be decreased when combined with Delavirdine.Approved
DeserpidineDeserpidine may increase the hypotensive activities of Sitaxentan.Approved
DiazoxideDiazoxide may increase the hypotensive activities of Sitaxentan.Approved
DihydralazineSitaxentan may increase the hypotensive activities of Dihydralazine.Investigational
DiltiazemDiltiazem may increase the hypotensive activities of Sitaxentan.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Sitaxentan.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Sitaxentan.Approved
EfavirenzThe metabolism of Sitaxentan can be decreased when combined with Efavirenz.Approved, Investigational
EfonidipineEfonidipine may increase the hypotensive activities of Sitaxentan.Approved
EnalaprilEnalapril may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
EnalaprilatEnalaprilat may increase the hypotensive activities of Sitaxentan.Approved
EpoprostenolEpoprostenol may increase the hypotensive activities of Sitaxentan.Approved
EprosartanEprosartan may increase the hypotensive activities of Sitaxentan.Approved
EtravirineThe metabolism of Sitaxentan can be decreased when combined with Etravirine.Approved
FelodipineFelodipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Sitaxentan.Approved
FloxuridineThe metabolism of Sitaxentan can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Sitaxentan can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Sitaxentan can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Sitaxentan can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Sitaxentan can be decreased when combined with Fluvoxamine.Approved, Investigational
FosinoprilFosinopril may increase the hypotensive activities of Sitaxentan.Approved
FosphenytoinThe metabolism of Sitaxentan can be increased when combined with Fosphenytoin.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
GemfibrozilThe metabolism of Sitaxentan can be decreased when combined with Gemfibrozil.Approved
GuanabenzGuanabenz may increase the hypotensive activities of Sitaxentan.Approved
GuanadrelGuanadrel may increase the hypotensive activities of Sitaxentan.Approved
GuanethidineGuanethidine may increase the hypotensive activities of Sitaxentan.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
HexamethoniumHexamethonium may increase the hypotensive activities of Sitaxentan.Experimental
HydracarbazineHydracarbazine may increase the hypotensive activities of Sitaxentan.Approved
HydralazineHydralazine may increase the hypotensive activities of Sitaxentan.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Sitaxentan.Approved
IloprostIloprost may increase the hypotensive activities of Sitaxentan.Approved, Investigational
ImidaprilSitaxentan may increase the hypotensive activities of Imidapril.Investigational
IndapamideIndapamide may increase the hypotensive activities of Sitaxentan.Approved
IndenololIndenolol may increase the hypotensive activities of Sitaxentan.Withdrawn
IndinavirThe metabolism of Sitaxentan can be decreased when combined with Indinavir.Approved
IndoraminIndoramin may increase the hypotensive activities of Sitaxentan.Withdrawn
IproclozideIproclozide may increase the hypotensive activities of Sitaxentan.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Sitaxentan.Withdrawn
IrbesartanThe metabolism of Sitaxentan can be decreased when combined with Irbesartan.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Sitaxentan.Approved
IsradipineIsradipine may increase the hypotensive activities of Sitaxentan.Approved
KetanserinSitaxentan may increase the hypotensive activities of Ketanserin.Investigational
KetoconazoleThe metabolism of Sitaxentan can be decreased when combined with Ketoconazole.Approved, Investigational
LabetalolLabetalol may increase the hypotensive activities of Sitaxentan.Approved
LacidipineLacidipine may increase the hypotensive activities of Sitaxentan.Approved
LatanoprostLatanoprost may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LeflunomideThe metabolism of Sitaxentan can be decreased when combined with Leflunomide.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LisinoprilLisinopril may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LofexidineLofexidine may increase the hypotensive activities of Sitaxentan.Approved, Investigational
LosartanThe metabolism of Sitaxentan can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Sitaxentan can be decreased when combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Sitaxentan can be decreased when it is combined with Lumacaftor.Approved
MacitentanSitaxentan may increase the hypotensive activities of Macitentan.Approved
ManidipineManidipine may increase the hypotensive activities of Sitaxentan.Approved
MebanazineMebanazine may increase the hypotensive activities of Sitaxentan.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Sitaxentan.Approved
MethyldopaMethyldopa may increase the hypotensive activities of Sitaxentan.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Sitaxentan.Investigational
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Sitaxentan.Approved, Investigational
MetipranololMetipranolol may increase the hypotensive activities of Sitaxentan.Approved
MetolazoneMetolazone may increase the hypotensive activities of Sitaxentan.Approved
MetoprololMetoprolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
MetyrosineSitaxentan may increase the hypotensive activities of Metyrosine.Approved
MibefradilMibefradil may increase the hypotensive activities of Sitaxentan.Withdrawn
MifepristoneThe serum concentration of Sitaxentan can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineMinaprine may increase the hypotensive activities of Sitaxentan.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Sitaxentan.Approved
MoclobemideMoclobemide may increase the hypotensive activities of Sitaxentan.Approved
MoexiprilMoexipril may increase the hypotensive activities of Sitaxentan.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Sitaxentan.Approved
MoxonidineMoxonidine may increase the hypotensive activities of Sitaxentan.Approved
NadololNadolol may increase the hypotensive activities of Sitaxentan.Approved
NaftopidilSitaxentan may increase the hypotensive activities of Naftopidil.Investigational
NebivololNebivolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
NialamideNialamide may increase the hypotensive activities of Sitaxentan.Withdrawn
NicardipineThe metabolism of Sitaxentan can be decreased when combined with Nicardipine.Approved
NicorandilNicorandil may increase the hypotensive activities of Sitaxentan.Approved
NiguldipineNiguldipine may increase the hypotensive activities of Sitaxentan.Experimental
NilvadipineNilvadipine may increase the hypotensive activities of Sitaxentan.Approved
NimodipineNimodipine may increase the hypotensive activities of Sitaxentan.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Sitaxentan.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Sitaxentan.Approved
NitroprussideNitroprusside may increase the hypotensive activities of Sitaxentan.Approved
ObinutuzumabSitaxentan may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Sitaxentan.Withdrawn
OlmesartanOlmesartan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Sitaxentan.Investigational
OmeprazoleThe metabolism of Sitaxentan can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OxprenololOxprenolol may increase the hypotensive activities of Sitaxentan.Approved
PargylinePargyline may increase the hypotensive activities of Sitaxentan.Approved
PenbutololPenbutolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
PentoliniumPentolinium may increase the hypotensive activities of Sitaxentan.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Sitaxentan.Approved, Investigational
PerindoprilPerindopril may increase the hypotensive activities of Sitaxentan.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Sitaxentan.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Sitaxentan.Withdrawn
PhenobarbitalThe metabolism of Sitaxentan can be increased when combined with Phenobarbital.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Sitaxentan.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Sitaxentan.Withdrawn
PhentolaminePhentolamine may increase the hypotensive activities of Sitaxentan.Approved
PhenytoinThe metabolism of Sitaxentan can be increased when combined with Phenytoin.Approved, Vet Approved
PinacidilPinacidil may increase the hypotensive activities of Sitaxentan.Withdrawn
PindololPindolol may increase the hypotensive activities of Sitaxentan.Approved
PirlindolePirlindole may increase the hypotensive activities of Sitaxentan.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Sitaxentan.Withdrawn
PolythiazidePolythiazide may increase the hypotensive activities of Sitaxentan.Approved
PrazosinPrazosin may increase the hypotensive activities of Sitaxentan.Approved
PrimidoneThe metabolism of Sitaxentan can be increased when combined with Primidone.Approved, Vet Approved
PropranololPropranolol may increase the hypotensive activities of Sitaxentan.Approved, Investigational
PyrimethamineThe metabolism of Sitaxentan can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinaprilQuinapril may increase the hypotensive activities of Sitaxentan.Approved, Investigational
QuinineQuinine may increase the hypotensive activities of Sitaxentan.Approved
RamiprilRamipril may increase the hypotensive activities of Sitaxentan.Approved
RasagilineRasagiline may increase the hypotensive activities of Sitaxentan.Approved
RemikirenRemikiren may increase the hypotensive activities of Sitaxentan.Approved
RescinnamineRescinnamine may increase the hypotensive activities of Sitaxentan.Approved
ReserpineReserpine may increase the hypotensive activities of Sitaxentan.Approved
RifampicinThe metabolism of Sitaxentan can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Sitaxentan can be increased when combined with Rifapentine.Approved
RilmenidineSitaxentan may increase the hypotensive activities of Rilmenidine.Investigational
RiociguatSitaxentan may increase the hypotensive activities of Riociguat.Approved
RituximabSitaxentan may increase the hypotensive activities of Rituximab.Approved
SafrazineSafrazine may increase the hypotensive activities of Sitaxentan.Withdrawn
SaprisartanSaprisartan may increase the hypotensive activities of Sitaxentan.Experimental
SecobarbitalThe metabolism of Sitaxentan can be increased when combined with Secobarbital.Approved, Vet Approved
SelegilineSelegiline may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Vet Approved
SelexipagSelexipag may increase the hypotensive activities of Sitaxentan.Approved
SildenafilSildenafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational
SorafenibThe metabolism of Sitaxentan can be decreased when combined with Sorafenib.Approved, Investigational
SpiraprilSpirapril may increase the hypotensive activities of Sitaxentan.Approved
SulfadiazineThe metabolism of Sitaxentan can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Sitaxentan can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Sitaxentan can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TadalafilTadalafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational
TelmisartanTelmisartan may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TemocaprilTemocapril may increase the hypotensive activities of Sitaxentan.Experimental, Investigational
TerlipressinTerlipressin may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TiboloneTibolone may increase the hypotensive activities of Sitaxentan.Approved
TicagrelorThe metabolism of Sitaxentan can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Sitaxentan can be decreased when combined with Ticlopidine.Approved
TicrynafenTicrynafen may increase the hypotensive activities of Sitaxentan.Withdrawn
TimololTimolol may increase the hypotensive activities of Sitaxentan.Approved
TofacitinibThe serum concentration of Tofacitinib can be increased when it is combined with Sitaxentan.Approved, Investigational
TolazolineTolazoline may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
TolbutamideThe metabolism of Sitaxentan can be decreased when combined with Tolbutamide.Approved
ToloxatoneToloxatone may increase the hypotensive activities of Sitaxentan.Approved
TorasemideTorasemide may increase the hypotensive activities of Sitaxentan.Approved
TrandolaprilTrandolapril may increase the hypotensive activities of Sitaxentan.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Sitaxentan.Experimental
TranylcypromineTranylcypromine may increase the hypotensive activities of Sitaxentan.Approved
TravoprostTravoprost may increase the hypotensive activities of Sitaxentan.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Sitaxentan.Approved, Investigational
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Sitaxentan.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Sitaxentan.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Sitaxentan.Approved
TrimethoprimThe metabolism of Sitaxentan can be decreased when combined with Trimethoprim.Approved, Vet Approved
UdenafilUdenafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational
UnoprostoneUnoprostone may increase the hypotensive activities of Sitaxentan.Approved
Valproic AcidThe metabolism of Sitaxentan can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Sitaxentan can be decreased when combined with Valsartan.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Sitaxentan.Approved
VinpocetineSitaxentan may increase the hypotensive activities of Vinpocetine.Investigational
VoriconazoleThe metabolism of Sitaxentan can be decreased when combined with Voriconazole.Approved, Investigational
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Sitaxentan.Approved
XylometazolineXylometazoline may increase the hypotensive activities of Sitaxentan.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Sitaxentan.Approved, Vet Approved
ZafirlukastThe metabolism of Sitaxentan can be decreased when combined with Zafirlukast.Approved, Investigational
Food Interactions
  • Take without regard to meals
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC02KX03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9811
Blood Brain Barrier+0.511
Caco-2 permeable-0.5662
P-glycoprotein substrateNon-substrate0.8285
P-glycoprotein inhibitor INon-inhibitor0.8519
P-glycoprotein inhibitor IINon-inhibitor0.8682
Renal organic cation transporterNon-inhibitor0.9158
CYP450 2C9 substrateNon-substrate0.8057
CYP450 2D6 substrateNon-substrate0.8266
CYP450 3A4 substrateNon-substrate0.5263
CYP450 1A2 substrateNon-inhibitor0.6693
CYP450 2C9 inhibitorInhibitor0.7225
CYP450 2D6 inhibitorNon-inhibitor0.8052
CYP450 2C19 inhibitorNon-inhibitor0.5
CYP450 3A4 inhibitorInhibitor0.925
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9157
Ames testNon AMES toxic0.634
CarcinogenicityNon-carcinogens0.5575
BiodegradationNot ready biodegradable0.9958
Rat acute toxicity2.5528 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9901
hERG inhibition (predictor II)Non-inhibitor0.9051
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral100 mg
Tablet, film coatedOral100 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2161346 No2004-11-232014-05-20Canada
CA2281090 No2005-06-072018-04-02Canada
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0181 mg/mLALOGPS
logP3.35ALOGPS
logP3.09ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)6.89ChemAxon
pKa (Strongest Basic)0.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area107.73 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity105.8 m3·mol-1ChemAxon
Polarizability43.12 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Dioxole is a five-membered unsaturated ring of two oxygen atoms and three carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodioxoles
Sub ClassNot Available
Direct ParentBenzodioxoles
Alternative Parents
Substituents
  • Benzodioxole
  • Aryl alkyl ketone
  • Aryl ketone
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Thiophene
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Oxazole
  • Isoxazole
  • Azole
  • Ketone
  • Oxacycle
  • Azacycle
  • Acetal
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
Gene Name:
EDNRA
Uniprot ID:
P25101
Molecular Weight:
48721.76 Da
References
  1. Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. [PubMed:17472992 ]
  2. Albertini M, Lafortuna CL, Ciminaghi B, Mazzola S, Clement MG: Endothelin involvement in respiratory centre activity. Prostaglandins Leukot Essent Fatty Acids. 2001 Sep;65(3):157-63. [PubMed:11728166 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  4. Kiowski W, Sutsch G, Oechslin E, Bertel O: Hemodynamic effects of bosentan in patients with chronic heart failure. Heart Fail Rev. 2001 Dec;6(4):325-34. [PubMed:11447307 ]
  5. Kramp R, Fourmanoir P, Caron N: Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1132-40. [PubMed:11704565 ]
  6. Martin C, Held HD, Uhlig S: Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):128-36. [PubMed:10961375 ]
  7. Sihvola RK, Pulkkinen VP, Koskinen PK, Lemstrom KB: Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. J Am Coll Cardiol. 2002 Feb 20;39(4):710-7. [PubMed:11849873 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Peptide hormone binding
Specific Function:
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name:
EDNRB
Uniprot ID:
P24530
Molecular Weight:
49643.255 Da
References
  1. Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. [PubMed:17472992 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. Gardiner SM, Kemp PA, March JE, Bennett T: Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Br J Pharmacol. 1994 Jul;112(3):823-30. [PubMed:7921608 ]
  4. Gupta SK, Saxena A, Singh U, Arya DS: Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. Mol Cell Biochem. 2005 Jul;275(1-2):67-74. [PubMed:16335785 ]
  5. Marano G, Palazzesi S, Bernucci P, Grigioni M, Formigari R, Ballerini L: ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits. Life Sci. 1998;63(18):PL259-66. [PubMed:9806221 ]
  6. Richard V, Kaeffer N, Hogie M, Tron C, Blanc T, Thuillez C: Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. Br J Pharmacol. 1994 Nov;113(3):869-76. [PubMed:7858879 ]
  7. Said SA, Ammar el SM, Suddek GM: Effect of bosentan (ETA/ETB receptor antagonist) on metabolic changes during stress and diabetes. Pharmacol Res. 2005 Feb;51(2):107-15. [PubMed:15629255 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. [PubMed:12065350 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Pulido T, Sandoval J, Roquet I, Gutierrez R, Rueda T, Pena H, Santos E, Miranda MT, Lupi E: Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8. doi: 10.1111/j.1365-2362.2009.02116.x. [PubMed:19335742 ]
  2. Opitz CF, Ewert R, Kirch W, Pittrow D: Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J. 2008 Aug;29(16):1936-48. doi: 10.1093/eurheartj/ehn234. Epub 2008 Jun 17. [PubMed:18562303 ]
  3. Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. [PubMed:12065350 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Stavros F, Kramer WG, Wilkins MR: The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects. Br J Clin Pharmacol. 2010 Jan;69(1):23-6. doi: 10.1111/j.1365-2125.2009.03541.x. [PubMed:20078609 ]
  2. Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. [PubMed:12065350 ]
Comments
comments powered by Disqus
Drug created on March 19, 2008 10:20 / Updated on August 17, 2016 12:24