Identification
- Summary
Selexipag is a non prostanoid IP prostacyclin receptor agonist used to treat pulmonary arterial hypertension.
- Brand Names
- Uptravi, Uptravi Titration Pack
- Generic Name
- Selexipag
- DrugBank Accession Number
- DB11362
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Selexipag (DB11362)
- Weight
- Average: 496.63
Monoisotopic: 496.2144267 - Chemical Formula
- C26H32N4O4S
- Synonyms
- Selexipag
- External IDs
- ACT-293987
- NS-304
Pharmacology
- Indication
Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Who group 1 pulmonary arterial hypertension •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
At the maximum tolerated dose of 1600 mcg twice per day, selexipag was not found to prolong the QT interval to a clinically relevant extent. Both selexipag and its metabolite caused concentration-dependent inhibition of platelet aggregation in vitro with IC50 of 5.5 µM and 0.21 µM, respectively. However, at clinically relevant concentrations, there was no effect on platelet aggregation test parameters following multiple dose administration of selexipag in healthy patients.
- Mechanism of action
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.
Target Actions Organism AProstacyclin receptor agonistHumans - Absorption
After oral administration, maximum concentrations of selexipag and its metabolite were observed to be reached at 1-3 and 3-4 hours, respectively. Absorption was impaired in the presence of food, resulting in delayed time to maximum concentration as well as ~30% lower peak plasma concentration. However, exposure was not found to be significantly affected by food.
- Volume of distribution
Not Available
- Protein binding
Both selexipag and its active metabolite are highly protein bound, approximately 99%.
- Metabolism
Selexipag yields its active metabolite by hydrolysis of the acylsulfonamide by the enzyme hepatic carboxylesterase 1. Oxidative metabolism catalyzed by CYP3A4 and CYP2C8 results in hydroxylated and dealkylated products. UGT1A3 and UGT2B7 are involved in the glucuronidation of the active metabolite. Other than active metabolite, other metabolites in circulation do not exceed 3% of the total drug-related material.
Hover over products below to view reaction partners
- Route of elimination
93% in feces, 12% in urine.
- Half-life
Selexipag's terminal half life is 0.8-2.5 hours. The active metabolite's terminal half life is 6.2-13.5 hours.
- Clearance
On average, 35 L/hour.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
A 40-70% increase in exposure was observed in subjects with severe renal impairment.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Selexipag. Abametapir The serum concentration of Selexipag can be increased when it is combined with Abametapir. Abatacept The metabolism of Selexipag can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Selexipag. Abiraterone The metabolism of Selexipag can be decreased when combined with Abiraterone. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Uptravi Tablet 1600 mcg Oral Janssen Pharmaceuticals 2016-04-21 Not applicable Canada 
Uptravi Tablet 1000 mcg Oral Janssen Pharmaceuticals 2016-04-21 Not applicable Canada Uptravi Tablet 400 mcg Oral Janssen Pharmaceuticals 2016-04-21 Not applicable Canada Uptravi Tablet, film coated 1600 μg Oral Janssen Cilag International Nv 2016-09-08 Not applicable EU 
Uptravi Tablet, coated 1600 ug/1 Oral Actelion Pharmaceuticals US, Inc. 2015-12-21 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image UPTRAVI Titration Pack Selexipag (200 ug/1) + Selexipag (800 ug/1) Kit; Tablet, coated Oral Actelion Pharmaceuticals US, Inc. 2015-12-21 Not applicable US UPTRAVI Titration Pack Selexipag (200 ug/1) + Selexipag (800 ug/1) Kit; Tablet, coated Oral Actelion Pharmaceuticals US, Inc. 2015-12-21 Not applicable US
Categories
- ATC Codes
- B01AC27 — Selexipag
- Drug Categories
- Acetates
- Acids, Acyclic
- Amides
- Antihypertensive Agents
- Blood and Blood Forming Organs
- Cardiovascular Agents
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Fatty Acids
- Fatty Acids, Volatile
- Lipids
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 substrates
- P-glycoprotein substrates
- Platelet Aggregation Inhibitors Excl. Heparin
- Prodrugs
- Prostacyclin Receptor Agonist
- Prostacyclin Receptor Agonists
- Receptors, Prostaglandin, agonists
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dialkylarylamines. These are aliphatic aromatic amines in which the amino group is linked to two aliphatic chains and one aromatic group.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Amines
- Direct Parent
- Dialkylarylamines
- Alternative Parents
- Aminopyrazines / Imidolactams / Benzene and substituted derivatives / Organosulfonic acids and derivatives / Heteroaromatic compounds / Aminosulfonyl compounds / Dialkyl ethers / Carboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds show 3 more
- Substituents
- Aminopyrazine / Aminosulfonyl compound / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Dialkyl ether / Dialkylarylamine / Ether show 14 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5EXC0E384L
- CAS number
- 475086-01-2
- InChI Key
- QXWZQTURMXZVHJ-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 2-{4-[(5,6-diphenylpyrazin-2-yl)(propan-2-yl)amino]butoxy}-N-methanesulfonylacetamide
- SMILES
- CC(C)N(CCCCOCC(=O)NS(C)(=O)=O)C1=NC(C2=CC=CC=C2)=C(N=C1)C1=CC=CC=C1
References
- General References
- Sharma K: Selexipag for the treatment of pulmonary arterial hypertension. Expert Rev Respir Med. 2016 Jan;10(1):1-3. doi: 10.1586/17476348.2016.1121103. Epub 2015 Dec 7. [Article]
- Kaufmann P, Okubo K, Bruderer S, Mant T, Yamada T, Dingemanse J, Mukai H: Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag. Am J Cardiovasc Drugs. 2015 Jun;15(3):195-203. doi: 10.1007/s40256-015-0117-4. [Article]
- FDA Approved Drug Products: UPTRAVI (selexipag) tablets and injection [Link]
- External Links
- KEGG Drug
- D09994
- PubChem Compound
- 9913767
- PubChem Substance
- 310265229
- ChemSpider
- 8089417
- BindingDB
- 50235383
- 1729002
- ChEBI
- 90844
- ChEMBL
- CHEMBL238804
- ZINC
- ZINC000003990451
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Selexipag
- FDA label
- Download (768 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Other Pulmonary Arterial Hypertension (PAH) 1 4 Recruiting Treatment Pulmonary Arterial Hypertension (PAH) 1 4 Terminated Treatment Pulmonary Arterial Hypertension (PAH) 1 3 Active Not Recruiting Treatment Pulmonary Hypertension (PH) 2 3 Completed Treatment Pulmonary Arterial Hypertension (PAH) 5
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 1800 ug/10mL Powder, for solution Intravenous 1800 ug/1 Tablet Oral 0.200 mg Tablet Oral 1000 mcg Tablet Oral 1200 mcg Tablet Oral 1400 mcg Tablet Oral 1600 mcg Tablet Oral 200 mcg Tablet Oral 400 mcg Tablet Oral 600 mcg Tablet Oral 800 mcg Tablet, coated Oral 1000 ug/1 Tablet, coated Oral 1200 ug/1 Tablet, coated Oral 1400 ug/1 Tablet, coated Oral 1600 ug/1 Tablet, coated Oral 200 ug/1 Tablet, coated Oral 400 ug/1 Tablet, coated Oral 600 ug/1 Tablet, coated Oral 800 ug/1 Tablet, film coated Oral 1000 μg Tablet, film coated Oral 1000 MICROGRAMMI Tablet, film coated Oral 1200 MICROGRAMMI Tablet, film coated Oral 1200 μg Tablet, film coated Oral 1400 MICROGRAMMI Tablet, film coated Oral 1400 μg Tablet, film coated Oral 1600 μg Tablet, film coated Oral 1600 MICROGRAMMI Tablet, film coated Oral 200 ?g Tablet, film coated Oral 200 MICROGRAMMI Tablet, film coated Oral 200 μg Tablet, film coated Oral 400 MICROGRAMMI Tablet, film coated Oral 400 μg Tablet, film coated Oral 600 MICROGRAMMI Tablet, film coated Oral 600 μg Tablet, film coated Oral 800 MICROGRAMMI Tablet, film coated Oral 800 μg Tablet, film coated Oral 1000 mcg Tablet, film coated Oral 1400 mcg Tablet, film coated Oral 1600 mcg Tablet, film coated Oral 200 mcg Tablet, film coated Oral Tablet, film coated Oral 400 mcg Tablet, film coated Oral 600 mcg Tablet, film coated Oral 800 mcg Tablet, film coated Oral 0.2 mg Tablet, film coated Oral 1.0 mg Tablet, film coated Oral 1.2 mg Tablet, film coated Oral 1.4 mg Tablet, film coated Oral 1.6 mg Tablet, film coated Oral 0.4 mg Tablet, film coated Oral 0.6 mg Tablet, film coated Oral 0.8 mg Kit; tablet, coated Oral Tablet, film coated Oral 1200 mcg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7205302 No 2007-04-17 2023-04-04 US US9173881 No 2015-11-03 2029-08-12 US US9284280 No 2016-03-15 2030-06-25 US US8791122 No 2014-07-29 2030-08-01 US US10828298 No 2020-11-10 2036-12-01 US US10821108 No 2020-11-03 2036-12-01 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00434 mg/mL ALOGPS logP 4.4 ALOGPS logP 3.76 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 3.77 Chemaxon pKa (Strongest Basic) 1.41 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 101.49 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 136.81 m3·mol-1 Chemaxon Polarizability 54.98 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-266e6c9785eb6236e66e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-fee8e92196287b7ce440 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0n2a-1109700000-51a85e5f15ad80b0e179 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004l-9201400000-2238a9c6084767897143 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0ue9-3019100000-15cbc766dc90a6aaa799 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9001000000-e6affec49f5a5c9c459f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 215.23659 predictedDeepCCS 1.0 (2019) [M+H]+ 217.63216 predictedDeepCCS 1.0 (2019) [M+Na]+ 224.31908 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Guanyl-nucleotide exchange factor activity
- Specific Function
- Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.
- Gene Name
- PTGIR
- Uniprot ID
- P43119
- Uniprot Name
- Prostacyclin receptor
- Molecular Weight
- 40955.485 Da
References
- Kaufmann P, Okubo K, Bruderer S, Mant T, Yamada T, Dingemanse J, Mukai H: Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag. Am J Cardiovasc Drugs. 2015 Jun;15(3):195-203. doi: 10.1007/s40256-015-0117-4. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Triglyceride lipase activity
- Specific Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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 un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Selexipag FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created at December 23, 2015 18:28 / Updated at February 20, 2024 23:55