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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

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

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

Targets

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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
UPTRAVI
PubMed

PubMed

TitleDatePubMed
An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.
1976 Oct 21
Prostanoid receptors and their biological actions.
1993
Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist.
2007 Dec 15
Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.
2007 Nov 1
2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug.
2007 Sep
Selexipag: a selective prostacyclin receptor agonist that does not affect rat gastric function.
2010 Oct
Pathways in pulmonary arterial hypertension: the future is here.
2012 Dec 1
Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag.
2015 Jun
Selexipag for the treatment of pulmonary arterial hypertension.
2016
Patents

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.
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:33:38 UTC 2019
Edited
by admin
on Mon Oct 21 21:33:38 UTC 2019
Record UNII
5EXC0E384L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SELEXIPAG
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
SELEXIPAG [USAN]
Common Name English
SELEXIPAG [WHO-DD]
Common Name English
SELEXIPAG [INN]
Common Name English
2-(4-((5,6-DIPHENYLPYRAZIN-2-YL)(PROPAN-2-YL)AMINO)BUTOXY)-N-(METHANESULFONYL)ACETAMIDE
Systematic Name English
SELEXIPAG [JAN]
Common Name English
UPTRAVI
Brand Name English
ACT-293987
Code English
NS-304
Code English
Classification Tree Code System Code
NDF-RT N0000192339
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
FDA ORPHAN DRUG 652018
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
WHO-ATC B01AC27
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
NCI_THESAURUS C78568
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
EMA ASSESSMENT REPORTS UPTRAVI (AUTHORIZED: HYPERTENSION, PULMONARY)
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
FDA ORPHAN DRUG 304810
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
Code System Code Type Description
RXCUI
1729002
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
ChEMBL
CHEMBL238804
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
PUBCHEM
9913767
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
NCI_THESAURUS
C152321
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
DRUG BANK
DB11362
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
CAS
475086-01-2
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
INN
9231
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
EVMPD
SUB130805
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY
EU-Orphan Drug
EU/3/05/316(WITHDRAWN)
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in February 2016 on request of the Sponsor, at the time of the granting of a marketing authorisation. On 26 August 2005, orphan designation (EU/3/05/316) was granted by the European Commission to Nippon Shinyaku Co. Ltd, Germany, for 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide for the treatment of pulmonary arterial hypertension and chronic thromoembolic pulmonary hypertension. The sponsorship was transferred to Actelion Registration Limited, United Kingdom, in February 2009. Update: 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide has been authorised in the EU as Uptravi since 12 May 2016. More information on Uptravi can be found in the European public assessment report (EPAR) on the Agency€s website.
NDF-RT
N0000020068
Created by admin on Mon Oct 21 21:33:38 UTC 2019 , Edited by admin on Mon Oct 21 21:33:38 UTC 2019
PRIMARY Prostacyclin Receptor Agonists [MoA]
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
IC50
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
IC50
EXCRETED UNCHANGED
No unchanged selexipag is excreted in the urine and feces.
FECAL; URINE
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> INHIBITOR
IC50
Related Record Type Details
METABOLITE ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION