Selexipag

Summary

Selexipag (CHEMBL238804) is an approved small-molecule orphan drug (ATC B01AC27) targeting PTGIR; indicated across 5 conditions including thrombotic disease and pulmonary arterial hypertension.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B01AC27
• Targets: 1 (PTGIR)
• Indications: 5 conditions
• Clinical trials: 23
• Chemistry: 496.6 Da · C26H32N4O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL238804
Name	Selexipag
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	9913767
ChEBI	CHEBI:90844
ATC	B01AC27
Molecular formula	C26H32N4O4S
Molecular weight	496.6
InChIKey	QXWZQTURMXZVHJ-UHFFFAOYSA-N

SMILES: CC(C)N(CCCCOCC(=O)NS(=O)(=O)C)C1=CN=C(C(=N1)C2=CC=CC=C2)C3=CC=CC=C3

IUPAC name: 2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]-N-methylsulfonylacetamide

ChEBI definition: A member of the class of pyrazines that is N-(methanesulfonyl)-2-{4-[(propan-2-yl)(pyrazin-2-yl)amino]butoxy}acetamide carrying two additional phenyl substituents at positions 5 and 6 on the pyrazine ring. An orphan drug used for the treatment of pulmonary arterial hypertension. It is a prodrug for ACT-333679 (the free carboxylic acid).

Pharmacological roles (ChEBI): orphan drug, prostacyclin receptor agonist, platelet aggregation inhibitor, vasodilator agent, prodrug.

Also known as: ACT-293987, NS-304, Selexipag, Uptravi, SELEXIPAG, selexipag

Patent coverage: 429 distinct patent families (1,018 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 762 (75%) 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
PTGIR	IP receptor	Agonist	6.59	0.2%	P43119

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Sodium channel protein type 5 subunit alpha, Prostacyclin receptor, Thromboxane A2 receptor, 5-hydroxytryptamine receptor 1A, Cannabinoid receptor 1, 5-hydroxytryptamine receptor 2A, Type-1 angiotensin II receptor, Alpha-1A adrenergic receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Adenosine receptor A3, 3’,5’-cyclic-AMP phosphodiesterase 4D, Androgen receptor, Prostacyclin receptor, Nuclear receptor subfamily 1 group I member 2, Prostaglandin D2 receptor, S-phase kinase-associated protein 2/Cyclin-dependent kinases regulatory subunit 1/S-phase kinase-associated protein 1, Bile salt export pump.

Bioactivity

ChEMBL activities: 11 potent at pChembl ≥ 5 of 22 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PTGIR	8.22	EC50	6	nM	CHEMBL_ACT_18017484
PTGIR	7.21	IC50	62	nM	CHEMBL_ACT_18017460
PTGDR	7	EC50	100	nM	CHEMBL_ACT_18017509
P43253	6.7	EC50	200	nM	CHEMBL_ACT_18017567
NR1I2	6.35	AC50	450	nM	CHEMBL_ACT_25224422
NR1I2	5.55	AC50	2791	nM	CHEMBL_ACT_25188306
PDE4D	5.32	AC50	4806	nM	CHEMBL_ACT_25185512
ABCB11	5.24	AC50	5700	nM	CHEMBL_ACT_25127089
PTGIR	5.19	IC50	6400	nM	CHEMBL_ACT_25048357
ADRA1A	5.14	AC50	7200	nM	CHEMBL_ACT_25218196
ADORA3	5.1	AC50	7890	nM	CHEMBL_ACT_25134390

Target pathways

Aggregated over 1 target gene(s): PTGIR.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Prostanoid ligand receptors	1	PTGIR
Prostacyclin signalling through prostacyclin receptor	1	PTGIR
G alpha (s) signalling events	1	PTGIR

Dominant GO biological processes

GO term	Targets
inflammatory response	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
cell-cell signaling	1
negative regulation of platelet-derived growth factor receptor signaling pathway	1
response to lipopolysaccharide	1
negative regulation of smooth muscle cell proliferation	1
signal transduction	1
G protein-coupled receptor signaling pathway	1

Indications & clinical

Indications

3 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
thrombotic disease	4	MONDO:0000831	HP:0004419
pulmonary arterial hypertension	4	MONDO:0015924	EFO:0001361
pulmonary hypertension	4	MONDO:0005149	MONDO:0005149

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 23.

Phase distribution

Phase	Trials
PHASE3	9
PHASE2	5
PHASE1	5
PHASE4	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05825417	PHASE4	RECRUITING	Pulmonary Hypertension: Intensification and Personalisation of Combination Rx
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT04175600	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension
NCT05179876	PHASE3	RECRUITING	A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option
NCT01106014	PHASE3	COMPLETED	Selexipag (ACT-293987) in Pulmonary Arterial Hypertension
NCT01112306	PHASE3	COMPLETED	ACT-293987 in Pulmonary Arterial Hypertension
NCT02471183	PHASE3	COMPLETED	Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension
NCT02558231	PHASE3	COMPLETED	The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
NCT03187678	PHASE3	COMPLETED	Safety Study of the Switch From Oral Selexipag to Intravenous Selexipag in Subjects With Stable Pulmonary Arterial Hypertension
NCT03689244	PHASE3	TERMINATED	A Study to Find Out if Selexipag is Effective and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension When the Disease is Inoperable or Persistent/Recurrent After Surgery and/or Interventional Treatment
NCT04565990	PHASE3	COMPLETED	A Study of Selexipag in Participants Who Participated in a Previous Selexipag Study
NCT03492177	PHASE2	ACTIVE_NOT_RECRUITING	A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension
NCT00993408	PHASE2	COMPLETED	Study of ACT-293987 (NS-304) in Pulmonary Arterial Hypertension (PAH)
NCT02260557	PHASE2	COMPLETED	Effects of Selexipag in Adults With Raynaud’s Phenomenon Secondary to Systemic Sclerosis
NCT03942211	PHASE2	TERMINATED	A Study in Participants With Sarcoidosis-associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag
NCT04589390	PHASE2	UNKNOWN	Selexipag for the Treatment of Schistosomiasis-Associated Pulmonary Arterial Hypertension
NCT02206204	PHASE1	COMPLETED	Study of Selexipag and Its Metabolite ACT-333679 on Cardiac Repolarization in Healthy Male and Female Subjects
NCT02206295	PHASE1	COMPLETED	Study in Healthy Male Subjects to Demonstrate Bioequivalence of 1600 μg Selexipag Administered as Eight Tablets of 200 μg or as Single Tablet of 1600 μg
NCT02770222	PHASE1	COMPLETED	A Clinical Study to Investigate the Effect of Gemfibrozil or Rifampicin on Blood Concentrations of Selexipag in Healthy Subjects
NCT02791815	PHASE1	COMPLETED	Potential Pharmacokinetic Interaction Between Selexipag and Midazolam in Healthy Male Subjects
NCT03496506	PHASE1	COMPLETED	A Clinical Study to Assess the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite in Healthy Male Subjects
NCT07356375	Not specified	NOT_YET_RECRUITING	Patient-Reported Outcomes and Adherence After Transition From Inhaled Iloprost to Oral Selexipag in Pulmonary Arterial Hypertension
NCT04914247	Not specified	APPROVED_FOR_MARKETING	Individual Patient Expanded Access IND for Selexipag (Uptravi) in Participants With Non-healing Wound, Buerger’s Disease

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

15 molecules share ≥1 primary target. Top 15 by shared-target count:

Molecule	Source	Status	Shared targets
ALPROSTADIL	ChEMBL + PubChem	Phase 4 (approved)	PTGIR
DINOPROSTONE	ChEMBL + PubChem	Phase 4 (approved)	PTGIR
ILOPROST	ChEMBL + PubChem	Phase 4 (approved)	PTGIR
TREPROSTINIL	ChEMBL + PubChem	Phase 4 (approved)	PTGIR
LAROPIPRANT	ChEMBL	Phase 4 (approved)	PTGIR
RALINEPAG	ChEMBL	Phase 3	PTGIR
TIMAPIPRANT	ChEMBL	Phase 3	PTGIR
BUTAPROST	ChEMBL	Phase 2	PTGIR
LASELIPAG	ChEMBL	Phase 2	PTGIR
Belzutifan	PubChem	Approved	PTGIR
Dinoprost	PubChem	Approved	PTGIR
epoprostenol	PubChem	Approved	PTGIR
Grapiprant	PubChem	Approved	PTGIR
Indomethacin	PubChem	Approved	PTGIR
Yohimbine	PubChem	Approved	PTGIR