Details of the Drug

General Information of Drug (ID: DMUTYR2)

Drug Name

Epoprostenol

Synonyms

Epoprostanol; Epoprostenolum; Flolan; PGX; Prostacyclin; Prostacycline; Prostacyclins; Vasocyclin; ProstaglandinI; Prostaglandin X; Prostaglandins X; PGI2; Prostacyclin I2; Prostaglandin I2; TRY 200; Epoprostenol (TN); Epoprostenol [USAN:INN]; Epoprostenolum [INN-Latin]; PG-I2; PGI(sub 2); Prostaglandin I(2); Try-200; U 53,217; U-53217; Epoprostenol (USAN/INN); KB-IV-24; (5E)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3R)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; (5Z)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; (5Z)-5-[(4R,5R)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; (5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate; (5Z,13E,15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoic acid; (5Z,9alpha,11alpha,13E,15S)-11,15-dihydroxy-6,9-epoxyprosta-5,13-dien-1-oic acid; (5Z,9alpha,11alpha,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid; (Z)-(3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-((E)-(3S)-3-hydroxy-1-octenyl)-2H-cyclopenta(b)furan-delta(sup 2,delta)-valeric acid; 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; 5-[5-hydroxy-4-(3-hydroxyoct-1-enyl)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; 6,9-alpha-Epoxy-11-alpha,15(S)-dihydroxyprosta-5(Z),13(E)-dien-1-oic acid

Indication

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

Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

352.5

Topological Polar Surface Area (xlogp)

2.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Half-life: The concentration or amount of drug in body reduced by one-half in less than 6 minutes [3]
Metabolism: The drug is metabolized via spontaneous degradation [4]
Vd: The volume of distribution (Vd) of drug is 0.357 L/kg [5]

Chemical Identifiers

Formula: C20H32O5
IUPAC Name: (5Z)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid
Canonical SMILES: CCCCC[C@@H](/C=C/[C@H]1[C@@H](C[C@H]2[C@@H]1C/C(=C/CCCC(=O)O)/O2)O)O
InChI: InChI=1S/C20H32O5/c1-2-3-4-7-14(21)10-11-16-17-12-15(8-5-6-9-20(23)24)25-19(17)13-18(16)22/h8,10-11,14,16-19,21-22H,2-7,9,12-13H2,1H3,(H,23,24)/b11-10+,15-8-/t14-,16+,17+,18+,19-/m0/s1
InChIKey: KAQKFAOMNZTLHT-OZUDYXHBSA-N

Cross-matching ID

PubChem CID: 5282411
ChEBI ID: CHEBI:15552
CAS Number: 35121-78-9
DrugBank ID: DB01240
TTD ID: D0V0IX
INTEDE ID: DR0593

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	[6], [7], [8]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)_{Main DME}	DE5IED8	CP2C9_HUMAN	Substrate	[9]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Pulmonary hypertension

ICD Disease Classification

BB01

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostacyclin receptor (PTGIR)	DTT	PTGIR	7.12E-02	-0.13	-0.33
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	2.25E-03	-4.98E-01	-6.49E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Epoprostenol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[28]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Levomilnacipran.	Chronic pain [MG30]	[29]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Epoprostenol and Regorafenib.	Colorectal cancer [2B91]	[30]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Epoprostenol and Ardeparin.	Coronary thrombosis [BA43]	[31]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Epoprostenol and Danaparoid.	Deep vein thrombosis [BD71]	[31]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Epoprostenol and Rivaroxaban.	Deep vein thrombosis [BD71]	[32]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Vilazodone.	Depression [6A70-6A7Z]	[29]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Vortioxetine.	Depression [6A70-6A7Z]	[29]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Epoprostenol and Isocarboxazid.	Depression [6A70-6A7Z]	[33]
Milnacipran	DMBFE74	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Milnacipran.	Depression [6A70-6A7Z]	[29]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Desvenlafaxine.	Depression [6A70-6A7Z]	[29]
Clomipramine	DMINRKW	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Clomipramine.	Depression [6A70-6A7Z]	[29]
Heme	DMGC287	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Heme.	Discovery agent [N.A.]	[34]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Epoprostenol and Apigenin.	Discovery agent [N.A.]	[35]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Epoprostenol and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[30]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Epoprostenol and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[36]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Epoprostenol and Ibrutinib.	Mature B-cell lymphoma [2A85]	[37]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Epoprostenol and Ponatinib.	Mature B-cell lymphoma [2A85]	[38]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Epoprostenol and Panobinostat.	Multiple myeloma [2A83]	[39]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Epoprostenol and Ozanimod.	Multiple sclerosis [8A40]	[33]
Dasatinib	DMJV2EK	Major	Increased risk of bleeding by the combination of Epoprostenol and Dasatinib.	Myeloproliferative neoplasm [2A20]	[40]
Omacetaxine mepesuccinate	DMPU2WX	Major	Increased risk of bleeding by the combination of Epoprostenol and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[41]
Prasugrel	DM7MT6E	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Prasugrel.	Myocardial infarction [BA41-BA43]	[28]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Vorapaxar.	Myocardial infarction [BA41-BA43]	[28]
Nepafenac	DMYK490	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Nepafenac.	Osteoarthritis [FA00-FA05]	[42]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Epoprostenol and MK-4827.	Ovarian cancer [2C73]	[30]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Epoprostenol and Safinamide.	Parkinsonism [8A00]	[33]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Epoprostenol and Rasagiline.	Parkinsonism [8A00]	[33]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[28]
Salsalate	DM13P4C	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Salsalate.	Rheumatoid arthritis [FA20]	[28]
Plicamycin	DM7C8YV	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Plicamycin.	Testicular cancer [2C80]	[28]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Caplacizumab.	Thrombocytopenia [3B64]	[28]
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Epoprostenol and Apixaban.	Thrombosis [DB61-GB90]	[30]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Cangrelor.	Thrombosis [DB61-GB90]	[28]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Epoprostenol and Brilinta.	Thrombosis [DB61-GB90]	[30]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Epoprostenol and Cabozantinib.	Thyroid cancer [2D10]	[43]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Epoprostenol and Betrixaban.	Venous thromboembolism [BD72]	[44]
-----------


⏷ Show the Full List of 37 DDI Information of This Drug

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: 1915).
2	Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
6	Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94.
7	Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem. 2002 Nov 29;277(48):46035-42.
8	Expression of human hexosaminidase-A phenotype depends on genes assigned to chromosomes 5 and 15. Birth Defects Orig Artic Ser. 1976;12(7):192-6.
9	Cytochrome P4502C9-derived epoxyeicosatrienoic acids induce the expression of cyclooxygenase-2 in endothelial cells. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):321-6.
10	Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
11	Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
12	Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
13	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
14	Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
15	Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
16	New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
17	A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
18	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
19	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.
20	Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80.
21	Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J Biol Chem. 2003 Feb 28;278(9):6947-58.
22	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.
23	Prostaglandin I2 IP Receptor Agonist, Beraprost, Prevents Transient Global Cerebral Ischemia Induced Hippocampal CA1 Injury in Aging Mice. J Neurol Disord. 2014;2:1000174.
24	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.
25	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
26	Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. Brain Res. 1997 Sep 26;769(2):321-8.
27	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.
28	Product Information. Flolan (epoprostenol). Glaxo Wellcome, Research Triangle Park, NC.
29	Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
30	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
31	Price AJ, Frcpath DO "Is there a clinical interaction between low molecular weight heparin and non-steroidal analgesics after total hip replacement?" Ann R Coll Surg Engl 77 (1995): 395. [PMID: 7486773]
32	Product Information. Xarelto (rivaroxaban). Bayer Inc, Toronto, IA.
33	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
34	Product Information. Panhematin (hemin). Recordati Rare Diseases Inc, Lebanon, NJ.
35	Heck AM, DeWitt BA, Lukes AL "Potential interactions between alternative therapies and warfarin." Am J Health Syst Pharm 57 (2000): 1221-7 quiz 1228-30. [PMID: 10902065]
36	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
37	Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
38	Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
39	Cerner Multum, Inc. "Australian Product Information.".
40	Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
41	Product Information. Brukinsa (zanubrutinib). BeiGene USA, Inc, San Mateo, CA.
42	Product Information. Acular (ketorolac). Allergan Inc, Irvine, CA.
43	Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
44	Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.