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Details

Stereochemistry ACHIRAL
Molecular Formula C26H32N4O4S
Molecular Weight 496.622
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SELEXIPAG

SMILES

CC(C)N(CCCCOCC(=O)NS(C)(=O)=O)C1=NC(C2=CC=CC=C2)=C(N=C1)C3=CC=CC=C3

InChI

InChIKey=QXWZQTURMXZVHJ-UHFFFAOYSA-N
InChI=1S/C26H32N4O4S/c1-20(2)30(16-10-11-17-34-19-24(31)29-35(3,32)33)23-18-27-25(21-12-6-4-7-13-21)26(28-23)22-14-8-5-9-15-22/h4-9,12-15,18,20H,10-11,16-17,19H2,1-3H3,(H,29,31)

HIDE SMILES / InChI

Description

Selexipag was approved by the United States FDA on December 22, 2015 for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization. PAH is a relatively rare disease with usually a poor prognosis requiring more treatment options to prolong long-term outcomes. Marketed by Actelion Pharmaceuticals under brand name Uptravi, selexipag and its active metabolite, ACT-333679 (MRE-269), act as agonists of the prostacyclin receptor to increase vasodilation in the pulmonary circulation and decrease elevated pressure in the blood vessels supplying blood to the lungs. Selexipag is a selective prostacyclin (IP, also called PGI2) receptor agonist. The key features of pulmonary arterial hypertension include a decrease in prostacyclin and prostacyclin synthase (enzyme that helps produce prostacyclin) in the lung. Prostacyclin is a potent vasodilator with anti-proliferative, anti-inflammatory, and anti-thrombotic effects; therefore, there is strong rationale for treatment with IP receptor agonists. Selexipag is chemically distinct as it is not PGI2 or a PGI2 analogue and has high selectivity for the IP receptor. It is metabolized by carboxylesterase 1 to yield an active metabolite (ACT-333679) that is approximately 37 times more potent than selexipag. Both selexipag and its metabolite are selective for the IP receptor over other prostanoid receptors. Selexipag is marketed under the brand name UPTRAVI, indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
5.5 µM [IC50]
4.0 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
UPTRAVI

Cmax

ValueDoseCo-administeredAnalytePopulation
5.29 ng/mL
600 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
1.85 ng/mL
200 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
4.12 ng/mL
400 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
5.98 ng/mL
400 μg single, oral
SELEXIPAG plasma
Homo sapiens
11.19 ng/mL
600 μg single, oral
SELEXIPAG plasma
Homo sapiens
11.53 ng/mL
800 μg single, oral
SELEXIPAG plasma
Homo sapiens
2.2 ng/mL
100 μg single, oral
SELEXIPAG plasma
Homo sapiens
3.4 ng/mL
200 μg single, oral
SELEXIPAG plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
13.78 ng × h/mL
600 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
5.38 ng × h/mL
200 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
9.7 ng × h/mL
400 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
12.35 ng × h/mL
400 μg single, oral
SELEXIPAG plasma
Homo sapiens
23.27 ng × h/mL
600 μg single, oral
SELEXIPAG plasma
Homo sapiens
24.97 ng × h/mL
800 μg single, oral
SELEXIPAG plasma
Homo sapiens
4.61 ng × h/mL
100 μg single, oral
SELEXIPAG plasma
Homo sapiens
6.77 ng × h/mL
200 μg single, oral
SELEXIPAG plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
1.24 h
600 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
1.14 h
200 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
1.41 h
400 μg 1 times / day steady-state, oral
SELEXIPAG plasma
Homo sapiens
1 h
400 μg single, oral
SELEXIPAG plasma
Homo sapiens
1.9 h
600 μg single, oral
SELEXIPAG plasma
Homo sapiens
2.3 h
800 μg single, oral
SELEXIPAG plasma
Homo sapiens
0.7 h
100 μg single, oral
SELEXIPAG plasma
Homo sapiens
0.8 h
200 μg single, oral
SELEXIPAG plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
, oral
SELEXIPAG plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
Starting dose: 200 mcg twice daily. Increase the dose by 200 mcg twice daily at weekly intervals to the highest tolerated dose up to 1600 mcg twice daily. Maintenance dose is determined by tolerability. Moderate hepatic impairment: Starting dose 200 mcg once daily, increase the dose by 200 mcg once daily at weekly intervals to the highest tolerated dose up to 1600 mcg.
Route of Administration: Oral
In Vitro Use Guide
Both selexipag and its active metabolite caused concentration-dependent inhibition of platelet aggregation in vitro with an IC50 of 5.5 uM and 0.21 uM, respectively.