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Identification
Name Iloprost
Accession Number DB01088 (APRD01027)
Type small molecule
Groups approved
Description

Iloprost is a synthetic analogue of prostacyclin PGI2. Iloprost dilates systemic and pulmonary arterial vascular beds. It is used to treat pulmonary arterial hypertension (PAH).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Ventavis
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
CAS number 78919-13-8
Weight Average: 478.6197
Monoisotopic: 478.271924326
Chemical Formula C30H38O5
InChI Key InChIKey=CZUMMMDKQYRZDP-JCAXBLPDSA-N
InChI
InChI=1S/C30H38O5/c1-3-4-10-21(2)27(31)16-15-25-26-18-22(17-24(26)19-28(25)32)11-8-9-14-30(34)35-20-29(33)23-12-6-5-7-13-23/h5-7,11-13,15-16,21,24-28,31-32H,8-10,14,17-20H2,1-2H3/b16-15+,22-11-
Plain Text
IUPAC Name
2-oxo-2-phenylethyl 5-[(2Z)-5-hydroxy-4-[(1E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl]-octahydropentalen-2-ylidene]pentanoate
SMILES
CC#CCC(C)C(O)\C=C\C1C(O)CC2C\C(CC12)=C\CCCC(=O)OCC(=O)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzoyl Derivatives
  • Cyclooctane and Derivatives
  • Acetophenones and Derivatives
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Alkynes
  • Ethers
  • Benzene and Derivatives
  • Aromatic compounds
  • Benzoyl Derivatives
  • Alcohols and Polyols
  • Cyclooctane and Derivatives
  • Acetophenones and Derivatives
  • Ketones
Pharmacology
Indication Used for the treatment of pulmonary arterial hypertension.
Pharmacodynamics Iloprost is a synthetic analogue of prostacyclin PGI2. Iloprost dilates systemic and pulmonary arterial vascular beds. It also affects platelet aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer.
Mechanism of action Iloprost is a second generation structural analog of prostacyclin (PGI) with about ten-fold greater potency than the first generation stable analogs, such as carbaprostacyclin. Iloprost binds with equal affinity to human prostacyclin (Prostanoid IP) and prostaglandin EP1 receptors. Iloprost constricts the ilium and fundus circular smooth muscle as strongly as prostaglandin E2 (PGE2) itself. Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets. In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time. All of these properties help to antagonize the pathological changes that take place in the small pulmonary arteries of patients with pulmonary hypertension.
Absorption Rapidly absorbed with bioavailability of 63%
Volume of distribution
  • 0.7 to 0.8 L/kg
Protein binding 60%
Metabolism Primarily hepatic. Iloprost is metabolized principally via beta-oxidation of the carboxyl side chain.
Route of elimination Not Available
Half life 20-30 minutes
Clearance
  • 20 mL/min/kg [Normal subjects]
Toxicity Overdoses can lead to hypotension, headache, flushing, nausea, vomiting, and diarrhea.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Actelion pharmaceuticals ltd
Packagers
Dosage forms
Form Route Strength
Solution Respiratory (inhalation)
Prices
Unit description Cost Unit
Ventavis 10 mcg/1 ml solution 74.4 USD ml
Ventavis 20 mcg/1 ml solution 74.4 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility Very slightly soluble Not Available
logP 4.8 Not Available
Predicted Properties
Property Value Source
water solubility 2.00e-03 g/l ALOGPS
logP 5.04 ALOGPS
logP 4.94 ChemAxon
logS -5.4 ALOGPS
pKa (strongest acidic) 13.72 ChemAxon
pKa (strongest basic) -0.87 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 83.83 ChemAxon
rotatable bond count 13 ChemAxon
refractivity 139.85 ChemAxon
polarizability 55.4 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 6443959 Link_out
PubChem Substance 46507818 Link_out
ChemSpider 4947911 Link_out
Therapeutic Targets Database DAP000273 Link_out
PharmGKB PA164746843 Link_out
RxList http://www.rxlist.com/cgi/generic4/ventavis.htm Link_out
Drugs.com http://www.drugs.com/cdi/iloprost.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Iloprost Link_out
ATC Codes
  • B01AC11
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (244 KB)
MSDS show (67.1 KB)
Interactions
Drug Interactions
Drug Interaction
Trandolapril The prostacyclin analogue, Iloprost, may increase the hypotensive effect of Trandolapril.
Food Interactions Not Available
Targets

1. Prostacyclin receptor

Pharmacological action: yes
Actions: agonist

Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase

Organism class: human
UniProt ID: P43119 Link_out
Gene: PTGIR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takamatsu H, Tsukada H, Watanabe Y, Cui Y, Kataoka Y, Hosoya T, Suzuki M, Watanabe Y: Specific ligand for a central type prostacyclin receptor attenuates neuronal damage in a rat model of focal cerebral ischemia. Brain Res. 2002 Jan 25;925(2):176-82. Pubmed
  2. Crutchley DJ, Solomon DE, Conanan LB: Prostacyclin analogues inhibit tissue factor expression in the human monocytic cell line THP-1 via a cyclic AMP-dependent mechanism. Arterioscler Thromb. 1992 Jun;12(6):664-70. Pubmed
  3. Schermuly RT, Pullamsetti SS, Breitenbach SC, Weissmann N, Ghofrani HA, Grimminger F, Nilius SM, Schror K, Kirchrath JM, Seeger W, Rose F: Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs. Respir Res. 2007 Jan 26;8:4. Pubmed
  4. Idzko M, Hammad H, van Nimwegen M, Kool M, Vos N, Hoogsteden HC, Lambrecht BN: Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. J Clin Invest. 2007 Feb;117(2):464-72. Pubmed
  5. Tsai AL, Vijjeswarapu H, Wu KK: Interaction between platelet receptor and iloprost isomers. Biochim Biophys Acta. 1988 Jul 21;942(2):220-6. Pubmed
  6. Olschewski H, Rose F, Schermuly R, Ghofrani HA, Enke B, Olschewski A, Seeger W: Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacol Ther. 2004 May;102(2):139-53. Pubmed
  7. Anderson JR, Nawarskas JJ: Pharmacotherapeutic management of pulmonary arterial hypertension. Cardiol Rev. 2010 May-Jun;18(3):148-62. Pubmed
  8. Mubarak KK: A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med. 2010 Jan;104(1):9-21. Epub 2009 Aug 15. Pubmed
  9. Krug S, Sablotzki A, Hammerschmidt S, Wirtz H, Seyfarth HJ: Inhaled iloprost for the control of pulmonary hypertension. Vasc Health Risk Manag. 2009;5(1):465-74. Pubmed

2. Prostaglandin E2 receptor, EP1 subtype

Pharmacological action: yes
Actions: agonist

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues

Organism class: human
UniProt ID: P34995 Link_out
Gene: PTGER1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sharif NA, Davis TL: Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand binding techniques. J Pharm Pharmacol. 2002 Apr;54(4):539-47. Pubmed
  2. Walch L, de Montpreville V, Brink C, Norel X: Prostanoid EP- and TP-receptors involved in the contraction of human pulmonary veins. Br J Pharmacol. 2001 Dec;134(8):1671-8. Pubmed

3. cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Pharmacological action: unknown
Actions: inducer

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate

Organism class: human
UniProt ID: P27815 Link_out
Gene: PDE4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wilkens H, Guth A, Konig J, Forestier N, Cremers B, Hennen B, Bohm M, Sybrecht GW: Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001 Sep 11;104(11):1218-22. Pubmed
  2. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Weissmann N, Schudt C, Tenor H, Seeger W, Grimminger F: Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. Crit Care Med. 2002 Nov;30(11):2489-92. Pubmed
  3. Schermuly RT, Leuchte H, Ghofrani HA, Weissmann N, Rose F, Kohstall M, Olschewski H, Schudt C, Grimminger F, Seeger W, Walmrath D: Zardaverine and aerosolised iloprost in a model of acute respiratory failure. Eur Respir J. 2003 Aug;22(2):342-7. Pubmed
  4. Grant PG, Mannarino AF, Colman RW: cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9071-5. Pubmed

4. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Pharmacological action: unknown
Actions: inducer

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents

Organism class: human
UniProt ID: Q07343 Link_out
Gene: PDE4B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wilkens H, Guth A, Konig J, Forestier N, Cremers B, Hennen B, Bohm M, Sybrecht GW: Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001 Sep 11;104(11):1218-22. Pubmed
  2. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Weissmann N, Schudt C, Tenor H, Seeger W, Grimminger F: Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. Crit Care Med. 2002 Nov;30(11):2489-92. Pubmed
  3. Schermuly RT, Leuchte H, Ghofrani HA, Weissmann N, Rose F, Kohstall M, Olschewski H, Schudt C, Grimminger F, Seeger W, Walmrath D: Zardaverine and aerosolised iloprost in a model of acute respiratory failure. Eur Respir J. 2003 Aug;22(2):342-7. Pubmed
  4. Grant PG, Mannarino AF, Colman RW: cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9071-5. Pubmed

5. cAMP-specific 3',5'-cyclic phosphodiesterase 4C

Pharmacological action: unknown
Actions: inducer

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate

Organism class: human
UniProt ID: Q08493 Link_out
Gene: PDE4C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wilkens H, Guth A, Konig J, Forestier N, Cremers B, Hennen B, Bohm M, Sybrecht GW: Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001 Sep 11;104(11):1218-22. Pubmed
  2. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Weissmann N, Schudt C, Tenor H, Seeger W, Grimminger F: Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. Crit Care Med. 2002 Nov;30(11):2489-92. Pubmed
  3. Schermuly RT, Leuchte H, Ghofrani HA, Weissmann N, Rose F, Kohstall M, Olschewski H, Schudt C, Grimminger F, Seeger W, Walmrath D: Zardaverine and aerosolised iloprost in a model of acute respiratory failure. Eur Respir J. 2003 Aug;22(2):342-7. Pubmed
  4. Grant PG, Mannarino AF, Colman RW: cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9071-5. Pubmed

6. cAMP-specific 3',5'-cyclic phosphodiesterase 4D

Pharmacological action: unknown
Actions: inducer

Regulates the levels of cAMP in the cell

Organism class: human
UniProt ID: Q08499 Link_out
Gene: PDE4D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wilkens H, Guth A, Konig J, Forestier N, Cremers B, Hennen B, Bohm M, Sybrecht GW: Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001 Sep 11;104(11):1218-22. Pubmed
  2. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Weissmann N, Schudt C, Tenor H, Seeger W, Grimminger F: Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. Crit Care Med. 2002 Nov;30(11):2489-92. Pubmed
  3. Schermuly RT, Leuchte H, Ghofrani HA, Weissmann N, Rose F, Kohstall M, Olschewski H, Schudt C, Grimminger F, Seeger W, Walmrath D: Zardaverine and aerosolised iloprost in a model of acute respiratory failure. Eur Respir J. 2003 Aug;22(2):342-7. Pubmed
  4. Grant PG, Mannarino AF, Colman RW: cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9071-5. Pubmed

7. Tissue-type plasminogen activator

Pharmacological action: unknown
Actions: other/unknown

Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Play a direct role in facilitating neuronal migration

Organism class: human
UniProt ID: P00750 Link_out
Gene: PLAT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kerins DM, Roy L, Kunitada S, Adedoyin A, FitzGerald GA, Fitzgerald DJ: Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue. Circulation. 1992 Feb;85(2):526-32. Pubmed
  2. Nicolini FA, Mehta JL, Nichols WW, Saldeen TG, Grant M: Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis. Circulation. 1990 Mar;81(3):1115-22. Pubmed
  3. Nichols WW, Nicolini FA, Saldeen TG, Mehta JL: Combined thrombolytic effects of tissue-plasminogen activator and a fibrinogen-degradation product peptide 6A or iloprost. J Cardiovasc Pharmacol. 1991 Aug;18(2):231-6. Pubmed
  4. Nizankowski R, Krzanowski M, Musial J, Szczeklik A: [Effect of thromboxane A2 synthetase inhibitor and prostacyclin analogue on arterial blood pressure, fibrinolysis and platelet function in patients with hypertension] Pol Tyg Lek. 1991 Jan 7-14;46(1-3):18-21. Pubmed
  5. Herczenik E, Bouma B, Korporaal SJ, Strangi R, Zeng Q, Gros P, Van Eck M, Van Berkel TJ, Gebbink MF, Akkerman JW: Activation of human platelets by misfolded proteins. Arterioscler Thromb Vasc Biol. 2007 Jul;27(7):1657-65. Epub 2007 May 17. Pubmed
Transporters

1. Solute carrier organic anion transporter family member 2B1

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost

UniProt ID: O94956 Link_out
Gene: SLCO2B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nishio T, Adachi H, Nakagomi R, Tokui T, Sato E, Tanemoto M, Fujiwara K, Okabe M, Onogawa T, Suzuki T, Nakai D, Shiiba K, Suzuki M, Ohtani H, Kondo Y, Unno M, Ito S, Iinuma K, Nunoki K, Matsuno S, Abe T: Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate. Biochem Biophys Res Commun. 2000 Sep 7;275(3):831-8. Pubmed

2. Solute carrier organic anion transporter family member 2A1

Actions: substrate

May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A

UniProt ID: Q92959 Link_out
Gene: SLCO2A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lu R, Kanai N, Bao Y, Schuster VL: Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9. Pubmed
  2. Kanai N, Lu R, Satriano JA, Bao Y, Wolkoff AW, Schuster VL: Identification and characterization of a prostaglandin transporter. Science. 1995 May 12;268(5212):866-9. Pubmed

3. Solute carrier organic anion transporter family member 3A1

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate (PubMed:10873595). Mediates transport of prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123 and vasopressin, but not DPDPE (a derivative of enkephalin lacking an N-terminal tyrosine residue), estrone-3- sulfate, taurocholate, digoxin nor DHEAS (PubMed:16971491)

UniProt ID: Q9UIG8 Link_out
Gene: SLCO3A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19