Details of the Drug

General Information of Drug (ID: DMVPZBE)

Drug Name

Iloprost

Synonyms

Ciloprost; Endoprost; Ilomedin; Ilomedine; Iloprostum; Ventavis; Iloprostum [Latin]; ZK 36374; E-1030; Iloprost (INN); Iloprost [BAN:INN]; SH-401; Ventavis (TN); ZK-36374; ZK-363775; [3H]-Iloprost; (16R,S)-Methyl-18,18,19,19-tetradehydro-6a-carbaprostaglandin I(sub 2); (5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxy-4-methyloct-1-en-6-ynyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid; (5E)-5-[(3aS,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl]hexahydropentalen-2(1H)-ylidene]pentanoic acid; (5E)-5-[(3aS,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxy-4-methyloct-1-en-6-ynyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid; (5Z)-5-[(3aS,5R,6aS)-5-hydroxy-4-[(E,3R)-3-hydroxy-4-methyloct-1-en-6-ynyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid; (E)-(3aS,4R,5R,6aS)-Hexahydro-5-hydroxy-4-((E)-(3S,4RS)-3-hydroxy-4-methyl-1-octen-6-ynyl)-delta(sup 2(1H),delta)-pentalenevaleric acid; (E)-5-(3aS,4R,5R,6aS)-5-Hydroxy-4((E)-(3S,4RS)-3-hydroxy-4-methyl-1-octen-6-inyl)perhydropentalen-2-yliden)valeriansaeure

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[1]
Pulmonary hypertension	BB01	Approved	[2]
Systemic sclerosis	4A42	Approved	[2]
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Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

360.5

Logarithm of the Partition Coefficient (xlogp)

2.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability: The bioavailability of drug is 63% []
Clearance: The clearance of drug is 20 mL/min/kg in healthy subjects []
Elimination: 0% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 20 - 30 minutes [4]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.0018 micromolar/kg/day [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.4% [4]
Vd: The volume of distribution (Vd) of drug is 0.7-0.8 L/kg []
Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [3]

Chemical Identifiers

Formula: C22H32O4
IUPAC Name: (5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxy-4-methyloct-1-en-6-ynyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid
Canonical SMILES: CC#CCC(C)[C@@H](/C=C/[C@H]1[C@@H](C[C@H]2[C@@H]1C/C(=C/CCCC(=O)O)/C2)O)O
InChI: InChI=1S/C22H32O4/c1-3-4-7-15(2)20(23)11-10-18-19-13-16(8-5-6-9-22(25)26)12-17(19)14-21(18)24/h8,10-11,15,17-21,23-24H,5-7,9,12-14H2,1-2H3,(H,25,26)/b11-10+,16-8+/t15?,17-,18+,19-,20+,21+/m0/s1
InChIKey: HIFJCPQKFCZDDL-ACWOEMLNSA-N

Cross-matching ID

PubChem CID: 5311181
ChEBI ID: CHEBI:63916
CAS Number: 78919-13-8
DrugBank ID: DB01088
TTD ID: D05ZTH
VARIDT ID: DR00099

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin E2 receptor EP2 (PTGER2)	TT1ZAVI	PE2R2_HUMAN	Agonist	[6]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 2A1 (SLCO2A1)	DT021JD	SO2A1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 3A1 (SLCO3A1)	DTVNRXW	SO3A1_HUMAN	Substrate	[8]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiopoietin-1 (ANGPT1)	OTVZ1NG3	ANGP1_HUMAN	Gene/Protein Processing	[9]
Angiopoietin-2 (ANGPT2)	OTEQK65P	ANGP2_HUMAN	Gene/Protein Processing	[9]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Gene/Protein Processing	[10]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Gene/Protein Processing	[9]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Gene/Protein Processing	[11]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Gene/Protein Processing	[11]
L-selectin (SELL)	OT6RAJZR	LYAM1_HUMAN	Gene/Protein Processing	[11]
Prostacyclin receptor (PTGIR)	OTWTABYM	PI2R_HUMAN	Protein Interaction/Cellular Processes	[12]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Pulmonary arterial hypertension

ICD Disease Classification

BB01.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin E2 receptor EP2 (PTGER2)	DTT	PTGER2	2.77E-06	1.15	1.37
Organic anion transporting polypeptide 3A1 (SLCO3A1)	DTP	OATP3A1	9.66E-01	2.27E-01	3.78E-01
Organic anion transporting polypeptide 2A1 (SLCO2A1)	DTP	OATP2A1	6.15E-01	-3.02E-02	-2.83E-02

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 Iloprost (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cilostazol	DMZMSCT	Moderate	Increased risk of bleeding by the combination of Iloprost and Cilostazol.	Arterial occlusive disease [BD40]	[13]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Iloprost and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[13]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Iloprost and Levomilnacipran.	Chronic pain [MG30]	[14]
Anisindione	DM2C48U	Moderate	Increased risk of bleeding by the combination of Iloprost and Anisindione.	Coagulation defect [3B10]	[13]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Iloprost and Regorafenib.	Colorectal cancer [2B91]	[15]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Iloprost and Ardeparin.	Coronary thrombosis [BA43]	[16]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Iloprost and Danaparoid.	Deep vein thrombosis [BD71]	[16]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Iloprost and Rivaroxaban.	Deep vein thrombosis [BD71]	[17]
Sertraline	DM0FB1J	Moderate	Increased risk of bleeding by the combination of Iloprost and Sertraline.	Depression [6A70-6A7Z]	[14]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Iloprost and Vilazodone.	Depression [6A70-6A7Z]	[14]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Iloprost and Isocarboxazid.	Depression [6A70-6A7Z]	[18]
Milnacipran	DMBFE74	Moderate	Increased risk of bleeding by the combination of Iloprost and Milnacipran.	Depression [6A70-6A7Z]	[14]
Escitalopram	DMFK9HG	Moderate	Increased risk of bleeding by the combination of Iloprost and Escitalopram.	Depression [6A70-6A7Z]	[14]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Iloprost and Desvenlafaxine.	Depression [6A70-6A7Z]	[14]
Clomipramine	DMINRKW	Moderate	Increased risk of bleeding by the combination of Iloprost and Clomipramine.	Depression [6A70-6A7Z]	[14]
Heme	DMGC287	Moderate	Increased risk of bleeding by the combination of Iloprost and Heme.	Discovery agent [N.A.]	[19]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Iloprost and Apigenin.	Discovery agent [N.A.]	[20]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Iloprost and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[15]
Sulfinpyrazone	DMEV954	Moderate	Increased risk of bleeding by the combination of Iloprost and Sulfinpyrazone.	Gout [FA25]	[13]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Iloprost and Procarbazine.	Hodgkin lymphoma [2B30]	[18]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Iloprost and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[21]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Iloprost and Ibrutinib.	Mature B-cell lymphoma [2A85]	[22]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Iloprost and Ponatinib.	Mature B-cell lymphoma [2A85]	[23]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Iloprost and Panobinostat.	Multiple myeloma [2A83]	[24]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Iloprost and Ozanimod.	Multiple sclerosis [8A40]	[18]
Fedratinib	DM4ZBK6	Moderate	Increased risk of bleeding by the combination of Iloprost and Fedratinib.	Myeloproliferative neoplasm [2A20]	[13]
Dasatinib	DMJV2EK	Major	Increased risk of bleeding by the combination of Iloprost and Dasatinib.	Myeloproliferative neoplasm [2A20]	[25]
Omacetaxine mepesuccinate	DMPU2WX	Major	Increased risk of bleeding by the combination of Iloprost and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[26]
Prasugrel	DM7MT6E	Moderate	Increased risk of bleeding by the combination of Iloprost and Prasugrel.	Myocardial infarction [BA41-BA43]	[13]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Iloprost and Vorapaxar.	Myocardial infarction [BA41-BA43]	[13]
Sibutramine	DMFJTDI	Moderate	Increased risk of bleeding by the combination of Iloprost and Sibutramine.	Obesity [5B80-5B81]	[14]
Dexfenfluramine	DMJ7YDS	Moderate	Increased risk of bleeding by the combination of Iloprost and Dexfenfluramine.	Obesity [5B80-5B81]	[14]
Nepafenac	DMYK490	Moderate	Increased risk of bleeding by the combination of Iloprost and Nepafenac.	Osteoarthritis [FA00-FA05]	[27]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Iloprost and MK-4827.	Ovarian cancer [2C73]	[15]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Iloprost and Safinamide.	Parkinsonism [8A00]	[18]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Iloprost and Rasagiline.	Parkinsonism [8A00]	[18]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Iloprost and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[13]
Salsalate	DM13P4C	Moderate	Increased risk of bleeding by the combination of Iloprost and Salsalate.	Rheumatoid arthritis [FA20]	[13]
Plicamycin	DM7C8YV	Moderate	Increased risk of bleeding by the combination of Iloprost and Plicamycin.	Testicular cancer [2C80]	[13]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Iloprost and Caplacizumab.	Thrombocytopenia [3B64]	[13]
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Iloprost and Apixaban.	Thrombosis [DB61-GB90]	[15]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Iloprost and Cangrelor.	Thrombosis [DB61-GB90]	[13]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Iloprost and Brilinta.	Thrombosis [DB61-GB90]	[15]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Iloprost and Cabozantinib.	Thyroid cancer [2D10]	[28]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Iloprost and Betrixaban.	Venous thromboembolism [BD72]	[29]
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References

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2	Iloprost FDA Label
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21	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
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23	Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
24	Cerner Multum, Inc. "Australian Product Information.".
25	Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
26	Product Information. Brukinsa (zanubrutinib). BeiGene USA, Inc, San Mateo, CA.
27	Product Information. Acular (ketorolac). Allergan Inc, Irvine, CA.
28	Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
29	Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.