Sitaxentan

Summary

Sitaxentan (CHEMBL282724) is an approved small molecule (ATC C02KX03) targeting EDNRA; indicated across 6 conditions including hypertensive disorder and pulmonary arterial hypertension.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02KX03
• Targets: 1 (EDNRA)
• Indications: 6 conditions
• Clinical trials: 16
• Chemistry: 454.9 Da · C18H15ClN2O6S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL282724
Name	Sitaxentan
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	216235
ATC	C02KX03
Molecular formula	C18H15ClN2O6S2
Molecular weight	454.9
InChIKey	PHWXUGHIIBDVKD-UHFFFAOYSA-N

SMILES: CC1=CC2=C(C=C1CC(=O)C3=C(C=CS3)S(=O)(=O)NC4=C(C(=NO4)C)Cl)OCO2

IUPAC name: N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide

Also known as: IPI-1040, Sitaxentan, Sitaxsentan, TBC-11251, SITAXENTAN, SITAXSENTAN, SID170465720, sitaxentan, TBC11251

Parent form; salt/anhydrous children: CHEMBL2105740

Patent coverage: 263 distinct patent families (639 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 498 (78%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EDNRA	ETA receptor	Antagonist	8	0.1%	P25101

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: ATP-binding cassette sub-family C member 4, Endothelin receptor type B, Endothelin-1 receptor, 3’,5’-cyclic-AMP phosphodiesterase 4A, Endothelin-1 receptor, ATP-binding cassette sub-family C member 3, Bile salt export pump.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EDNRA	9.37	Ki	0.43	nM	CHEMBL_ACT_1267383
P26684	9.37	Ki	0.43	nM	CHEMBL_ACT_169943
EDNRA	9.37	Ki	0.43	nM	CHEMBL_ACT_26274408
EDNRA	8.85	IC50	1.4	nM	CHEMBL_ACT_1267377
EDNRA	8.85	IC50	1.4	nM	CHEMBL_ACT_161317
EDNRA	8.85	IC50	1.4	nM	CHEMBL_ACT_169939
EDNRA	8.85	IC50	1.4	nM	CHEMBL_ACT_776102
EDNRB	5.01	IC50	9800	nM	CHEMBL_ACT_1267378
ABCB11	5.01	AC50	9700	nM	CHEMBL_ACT_25127151

Target pathways

Aggregated over 1 target gene(s): EDNRA.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	1	EDNRA
G alpha (q) signalling events	1	EDNRA

Dominant GO biological processes

GO term	Targets
mitotic cell cycle	1
branching involved in blood vessel morphogenesis	1
response to hypoxia	1
in utero embryonic development	1
blood vessel remodeling	1
response to amphetamine	1
regulation of heart rate	1
glomerular filtration	1
cardiac chamber formation	1
left ventricular cardiac muscle tissue morphogenesis	1
atrial cardiac muscle tissue development	1
cardiac neural crest cell migration involved in outflow tract morphogenesis	1
noradrenergic neuron differentiation	1
intracellular calcium ion homeostasis	1
smooth muscle contraction	1

Indications & clinical

Indications

6 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
hypertensive disorder	4	MONDO:0005044	EFO:0000537
pulmonary arterial hypertension	3	MONDO:0015924	EFO:0001361
pulmonary hypertension	3	MONDO:0005149	MONDO:0005149
chronic kidney disease	2	MONDO:0005300	EFO:0003884
proteinuria	2	MONDO:0003634	HP:0000093
asthma	2	MONDO:0004979	MONDO:0004979

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE3	7
PHASE2	3
PHASE1	3
PHASE2/PHASE3	1
EARLY_PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00034307	PHASE2/PHASE3	UNKNOWN	Safety and Efficacy of Sitaxsentan in the Treatment of Pulmonary Arterial Hypertension
NCT00080457	PHASE3	COMPLETED	Safety and Efficacy Study of Sitaxentan Sodium (Thelin™) in Patients With Pulmonary Arterial Hypertension
NCT00795639	PHASE3	TERMINATED	Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil (SR-PAAS)
NCT00796510	PHASE3	TERMINATED	Study Providing Monotherapy (Sitaxsentan) And Combination Therapy (Sitaxsentan+Sildenafil) To Subjects With Pulmonary Arterial Hypertension (PAH) To Assess Long-Term Safety
NCT00796666	PHASE3	TERMINATED	Study Looking at Combination Therapy (Sitaxsentan+Sildenafil) Vs. Monotherapy (Sitaxsentan Alone) SR-PAAS -Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil
NCT00811018	PHASE3	TERMINATED	A Long-Term, Open-Label Study to Evaluate the Safety of Sitaxsentan Sodium Treatment in Patients With Pulmonary Arterial Hypertension
NCT01204853	PHASE3	TERMINATED	A 12 Week Safety And Efficacy Study Of Sitaxentan Sodium In Japanese Pulmonary Arterial Hypertension Patients
NCT01210443	PHASE3	TERMINATED	Long-Term Open-Label, Safety Study Of Sitaxentan Sodium In Japanese Pulmonary Arterial Hypertension Patients
NCT00817037	PHASE2	COMPLETED	Sitaxsentan in Proteinuric Chronic Kidney Disease
NCT00838383	PHASE2	COMPLETED	Confirming The Sitaxsentan Dose In Patients Undergoing Heart Surgery
NCT01050491	PHASE2	TERMINATED	Study on the Effects of Sitaxsentan on Airway Remodeling in Patients With Severe Asthma
NCT01244620	PHASE1	TERMINATED	A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
NCT01251835	PHASE1	WITHDRAWN	Effect Of Rifampin On Pharmacokinetics Of Sitaxsentan
NCT01251848	PHASE1	WITHDRAWN	Drug Interaction Between Ritonavir And Sitaxsentan
NCT01100736	EARLY_PHASE1	COMPLETED	Role of Endothelin-A (ETA) and Endothelin-B (ETB) Receptors in the Vasodilatory Response to Endothelin-3 (ET-3)
NCT00593905	Not specified	WITHDRAWN	Pharmacogenomics in Pulmonary Arterial Hypertension

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

41 molecules share ≥1 primary target. Top 41 by shared-target count:

Molecule	Source	Status	Shared targets
BOSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA
SPARSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA
ACYCLOVIR	ChEMBL	Phase 4 (approved)	EDNRA
AMBRISENTAN	ChEMBL	Phase 4 (approved)	EDNRA
AMIODARONE	ChEMBL	Phase 4 (approved)	EDNRA
APROCITENTAN	ChEMBL	Phase 4 (approved)	EDNRA
ENOXACIN	ChEMBL	Phase 4 (approved)	EDNRA
FLUOXETINE	ChEMBL	Phase 4 (approved)	EDNRA
GRAMICIDIN	ChEMBL	Phase 4 (approved)	EDNRA
IRBESARTAN	ChEMBL	Phase 4 (approved)	EDNRA
MACITENTAN	ChEMBL	Phase 4 (approved)	EDNRA
MELOXICAM	ChEMBL	Phase 4 (approved)	EDNRA
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	EDNRA
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	EDNRA
SULFATHIAZOLE	ChEMBL	Phase 4 (approved)	EDNRA
SULFISOXAZOLE	ChEMBL	Phase 4 (approved)	EDNRA
SUNITINIB	ChEMBL	Phase 4 (approved)	EDNRA
ATRASENTAN	ChEMBL	Phase 3	EDNRA
AVOSENTAN	ChEMBL	Phase 3	EDNRA
CLAZOSENTAN	ChEMBL	Phase 3	EDNRA
DARUSENTAN	ChEMBL	Phase 3	EDNRA
EXISULIND	ChEMBL	Phase 3	EDNRA
TEZOSENTAN	ChEMBL	Phase 3	EDNRA
ZIBOTENTAN	ChEMBL	Phase 3	EDNRA
BQ-123	ChEMBL	Phase 2	EDNRA
EDONENTAN	ChEMBL	Phase 2	EDNRA
ENDOTHELIN	ChEMBL	Phase 2	EDNRA
ENRASENTAN	ChEMBL	Phase 2	EDNRA
FANDOSENTAN	ChEMBL	Phase 2	EDNRA
FELOPRENTAN	ChEMBL	Phase 2	EDNRA
Afatinib	PubChem	Approved	EDNRA
Apixaban	PubChem	Approved	EDNRA
Binimetinib	PubChem	Approved	EDNRA
chenodiol	PubChem	Approved	EDNRA
Dihydroergotamine	PubChem	Approved	EDNRA
Fidaxomicin	PubChem	Approved	EDNRA
Fulvestrant	PubChem	Approved	EDNRA
Imipenem	PubChem	Approved	EDNRA
Propoxyphene	PubChem	Approved	EDNRA
Pyrazinamide	PubChem	Approved	EDNRA
Tafamidis	PubChem	Approved	EDNRA