Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMAHSU0)

• Drug Name: Selexipag Drug Info
• Synonyms: Selexipag; NS-304; 475086-01-2; Uptravi; NS 304; ACT-293987; UNII-5EXC0E384L; Selexipag(NS-304); ACT 293987; 5EXC0E384L; 2-(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)-N-(methylsulfonyl)acetamide; 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide; 2-(4-((5,6-Diphenylpyrazin-2-yl)(propan-2-yl)amino)butoxy}-n-(methanesulfonyl)acetamide; Selexipag [USAN:INN]; 2-{4-[(5,6-diphenylpyrazin-2-yl)(propan-2-yl)amino]butoxy}-N-(methanesulfonyl)acetamide; Uptravi (TN)

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[1] , [2]

• Cross-matching ID:
  PubChem CID: 9913767
  ChEBI ID: CHEBI:90844
  CAS Number: CAS 475086-01-2
  TTD Drug ID: DMAHSU0
  INTEDE Drug ID: DR1471
  ACDINA Drug ID: D00619

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[6]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[6]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[7]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[8]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[9]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[10]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[6]
Mycophenolate mofetil	DMPQAGE	Organ transplant rejection	NE84	Approved	[11]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[12]

Drug(s) Targeting Prostacyclin receptor (PTGIR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Treprostinil	DMTIQF3	Pulmonary arterial hypertension	BB01.0	Approved	[13]
Epoprostenol	DMUTYR2	Pulmonary hypertension	BB01	Approved	[14]
Dinoprost Tromethamine	DMXQKSL	Abortion	JA00	Approved	[15]
Misoprostol	DMHVJFK	Medical abortion	JA00.1Z	Approved	[15]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[16]
Beraprost	DMWL182	Pulmonary hypertension	BB01	Phase 4	[17]
esuberaprost	DMXLGED	Gout	FA25	Phase 3	[18]
Ralinepag	DM7G4Y9	Pulmonary arterial hypertension	BB01.0	Phase 2	[19]
Clinprost	DM6E5VA	Asthma	CA23	Discontinued in Preregistration	[20]
Ataprost	DMPTG39	Asthma	CA23	Discontinued in Phase 3	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostacyclin receptor (PTGIR)	TTOFYT1	PI2R_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C8 (CYP2C8) Main DME	DES5XRU	CP2C8_HUMAN	Substrate	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7552).
• [2] ClinicalTrials.gov (NCT01106014) Selexipag (ACT-293987) in Pulmonary Arterial Hypertension, GRIPHON Trial. U.S. National Institutes of Health.
• [3] Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80.
• [4] FDA Label of Uptravi. The 2020 official website of the U.S. Food and Drug Administration.
• [5] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [6] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [7] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [8] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [9] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [10] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [11] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [12] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [13] Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J. 2009 Apr;157(4):625-35.
• [14] Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94.
• [15] Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J Biol Chem. 2003 Feb 28;278(9):6947-58.
• [16] Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
• [17] Prostaglandin I2 IP Receptor Agonist, Beraprost, Prevents Transient Global Cerebral Ischemia Induced Hippocampal CA1 Injury in Aging Mice. J Neurol Disord. 2014;2:1000174.
• [18] Specific binding of the new stable epoprostenol analogue beraprost sodium to prostacyclin receptors on human and rat platelets. Arzneimittelforschung. 1989 Apr;39(4):495-9.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. Brain Res. 1997 Sep 26;769(2):321-8.
• [21] Pharmacokinetics of intravenous ataprost alfadex, a new prostaglandin I2 analog in healthy volunteers. Int J Clin Pharmacol Ther Toxicol. 1993 Aug;31(8):373-5.