Identification

Name
Iloprost
Accession Number
DB01088  (APRD01027)
Type
Small Molecule
Groups
Approved, Investigational
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
Synonyms
  • Iloprost
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution0.01 mg/1mLRespiratory (inhalation)Actelion2005-05-07Not applicableUs
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution10 ug/1mLRespiratory (inhalation)CoTherix, Inc.2006-05-102006-05-10Us
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution20 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2003-09-16Not applicableEu
Categories
UNII
JED5K35YGL
CAS number
78919-13-8
Weight
Average: 360.494
Monoisotopic: 360.23005951
Chemical Formula
C22H32O4
InChI Key
HIFJCPQKFCZDDL-ACWOEMLNSA-N
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
IUPAC Name
5-[(2E,3aS,4R,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl]-octahydropentalen-2-ylidene]pentanoic acid
SMILES
[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)C(C)CC#CC)[C@@]1([H])C\C(C2)=C\CCCC(O)=O

Pharmacology

Indication

Used for the treatment of pulmonary arterial hypertension.

Associated Conditions
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.

TargetActionsOrganism
AProstacyclin receptor
agonist
Human
AProstaglandin E2 receptor EP1 subtype
agonist
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4A
inducer
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4B
inducer
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4C
inducer
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4D
inducer
Human
UTissue-type plasminogen activator
other/unknown
Human
UProstaglandin D2 receptor 2
agonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Iloprost can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Iloprost is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Iloprost is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidIloprost may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-TestosteroneThe therapeutic efficacy of Iloprost can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Iloprost can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Iloprost is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Iloprost can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Iloprost can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Iloprost.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
5311181
PubChem Substance
46507818
ChemSpider
4470703
BindingDB
23954
ChEBI
63916
ChEMBL
CHEMBL494
Therapeutic Targets Database
DAP000273
PharmGKB
PA164746843
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Iloprost
ATC Codes
B01AC11 — Iloprost
FDA label
Download (244 KB)
MSDS
Download (67.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedNot AvailableAsthma Bronchial1
1CompletedTreatmentAcute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS) / Pulmonary Hypertension (PH)1
1RecruitingPreventionCytologic Atypia / Former Smoker / Lung, Carcinoma / Mild Dysplasia / Precancerous Conditions1
1Unknown StatusBasic ScienceHypoxic Pulmonary Vasoconstriction1
1WithdrawnBasic ScienceHypoxic Pulmonary Vasoconstriction1
1, 2CompletedTreatmentHealthy Volunteers1
1, 2CompletedTreatmentMyocardial Infarction1
1, 2WithdrawnTreatmentAcute Respiratory Distress Syndrome (ARDS) / Defect, Congenital Heart / Neonatal Hypoxic Respiratory Failure / Persistent Pulmonary Hypertension of Newborn (PPHN) / Pulmonary Hypertension (PH)1
2CompletedBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
2CompletedPreventionLung Cancers / Precancerous Conditions1
2CompletedTreatmentAyerza Syndrome / Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)1
2CompletedTreatmentCardiac Arrest1
2CompletedTreatmentPulmonary Fibrosis / Pulmonary Hypertension (PH)1
2CompletedTreatmentPulmonary Hypertension (PH)2
2RecruitingTreatmentResidual Pulmonary Hypertension1
2TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
2TerminatedTreatmentPulmonary Hypertension (PH)1
2TerminatedTreatmentSclerosis, Progressive Systemic1
2Unknown StatusTreatmentShock, Septic1
2WithdrawnTreatmentPulmonary Arterial Hypertension (PAH)1
2, 3CompletedPreventionAngioplasty, Transluminal, Percutaneous Coronary / Coronary Angiography / Renal Insufficiency,Chronic1
3CompletedTreatmentPulmonary Arterial Hypertension (PAH)2
3CompletedTreatmentPulmonary Hypertension (PH)4
3CompletedTreatmentRaynaud's Disease / Sclerosis, Progressive Systemic1
3Not Yet RecruitingTreatmentRespiratory Distress Syndrome, Adult1
3TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
3TerminatedTreatmentPulmonary Hypertension (PH)1
3Unknown StatusTreatmentPulmonary Arterial Hypertension (PAH)1
4CompletedNot AvailableHypertension,Essential1
4CompletedTreatmentPeripheral Arterial Disease (PAD)1
4CompletedTreatmentPulmonary Arterial Hypertension (PAH) / Sarcoidosis1
4RecruitingDiagnosticPulmonary Hypertension (PH)1
4RecruitingTreatmentHeart Failure With Normal Ejection Fraction1
4RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
4TerminatedTreatmentPulmonary Hypertension (PH)2
Not AvailableCompletedNot AvailablePeripheral Arterial Disease (PAD)1
Not AvailableCompletedNot AvailablePulmonary Arterial Hypertension (PAH)3
Not AvailableCompletedNot AvailablePulmonary Hypertension (PH)6
Not AvailableCompletedBasic SciencePulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)1
Not AvailableCompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
Not AvailableCompletedTreatmentInsulin Sensitivity/Resistance / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentLung Cancers1
Not AvailableRecruitingNot AvailablePulmonary Hypertension (PH)2
Not AvailableTerminatedNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableTerminatedTreatmentCongenital Heart Disease (CHD) / Eisenmenger's Syndrome / Pulmonary Arterial Hypertension (PAH)1
Not AvailableUnknown StatusNot AvailablePregnancy1
Not AvailableWithdrawnTreatmentPersistent Pulmonary Hypertension / Respiratory Distress Syndrome (RDS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actelion Pharmaceuticals Inc.
  • Berlimed Sa
  • Cotherix Inc.
Dosage forms
FormRouteStrength
SolutionRespiratory (inhalation)0.01 mg/1mL
SolutionRespiratory (inhalation)0.02 mg/1mL
SolutionRespiratory (inhalation)10 μg/ml
SolutionRespiratory (inhalation)10 ug/1mL
SolutionRespiratory (inhalation)20 μg/ml
Prices
Unit descriptionCostUnit
Ventavis 10 mcg/1 ml solution74.4USD ml
Ventavis 20 mcg/1 ml solution74.4USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityVery slightly solubleNot Available
logP4.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00874 mg/mLALOGPS
logP4.22ALOGPS
logP3.56ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)4.66ChemAxon
pKa (Strongest Basic)-0.87ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area77.76 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity105.18 m3·mol-1ChemAxon
Polarizability42.68 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9543
Blood Brain Barrier+0.5506
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.7459
P-glycoprotein inhibitor INon-inhibitor0.6507
P-glycoprotein inhibitor IINon-inhibitor0.8227
Renal organic cation transporterNon-inhibitor0.8698
CYP450 2C9 substrateNon-substrate0.8526
CYP450 2D6 substrateNon-substrate0.8946
CYP450 3A4 substrateSubstrate0.6553
CYP450 1A2 substrateNon-inhibitor0.5515
CYP450 2C9 inhibitorNon-inhibitor0.7963
CYP450 2D6 inhibitorNon-inhibitor0.8072
CYP450 2C19 inhibitorNon-inhibitor0.719
CYP450 3A4 inhibitorInhibitor0.5377
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7556
Ames testNon AMES toxic0.7104
CarcinogenicityNon-carcinogens0.9587
BiodegradationNot ready biodegradable0.6052
Rat acute toxicity2.7260 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9288
hERG inhibition (predictor II)Non-inhibitor0.6964
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Eicosanoids
Direct Parent
Prostaglandins and related compounds
Alternative Parents
Bicyclic monoterpenoids / Medium-chain hydroxy acids and derivatives / Fatty alcohols / Medium-chain fatty acids / Hydroxy fatty acids / Branched fatty acids / Secondary alcohols / Cyclic alcohols and derivatives / Monocarboxylic acids and derivatives / Carboxylic acids
show 3 more
Substituents
Prostaglandin skeleton / Bicyclic monoterpenoid / Monoterpenoid / Fatty alcohol / Medium-chain hydroxy acid / Medium-chain fatty acid / Branched fatty acid / Hydroxy fatty acid / Cyclic alcohol / Secondary alcohol
show 10 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
monocarboxylic acid, secondary alcohol, carbobicyclic compound (CHEBI:63916)

Targets

Kind
Protein
Organism
Human
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
  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:11792366]
  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:1375507]
  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:17257398]
  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:17273558]
  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:2456096]
  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:15163595]
  7. Anderson JR, Nawarskas JJ: Pharmacotherapeutic management of pulmonary arterial hypertension. Cardiol Rev. 2010 May-Jun;18(3):148-62. doi: 10.1097/CRD.0b013e3181d4e921. [PubMed:20395700]
  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. doi: 10.1016/j.rmed.2009.07.015. Epub 2009 Aug 15. [PubMed:19683911]
  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:19475782]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Prostaglandin e receptor activity
Specific Function
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 importa...
Gene Name
PTGER1
Uniprot ID
P34995
Uniprot Name
Prostaglandin E2 receptor EP1 subtype
Molecular Weight
41800.655 Da
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:11999132]
  2. Walch L, de Montpreville V, Brink C, Norel X: Prostanoid EP(1)- and TP-receptors involved in the contraction of human pulmonary veins. Br J Pharmacol. 2001 Dec;134(8):1671-8. [PubMed:11739243]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Metal ion binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name
PDE4A
Uniprot ID
P27815
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Molecular Weight
98142.155 Da
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:11551870]
  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:12441759]
  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:12952271]
  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:2461561]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Metal ion binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging f...
Gene Name
PDE4B
Uniprot ID
Q07343
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Molecular Weight
83342.695 Da
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:11551870]
  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:12441759]
  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:12952271]
  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:2461561]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Metal ion binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name
PDE4C
Uniprot ID
Q08493
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Molecular Weight
79900.795 Da
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:11551870]
  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:12441759]
  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:12952271]
  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:2461561]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Ubiquitin protein ligase binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name
PDE4D
Uniprot ID
Q08499
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Molecular Weight
91114.1 Da
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:11551870]
  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:12441759]
  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:12952271]
  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:2461561]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Serine-type endopeptidase activity
Specific Function
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 t...
Gene Name
PLAT
Uniprot ID
P00750
Uniprot Name
Tissue-type plasminogen activator
Molecular Weight
62916.495 Da
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:1370924]
  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:1689620]
  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:1717784]
  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:1726988]
  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:17510465]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Prostaglandin j receptor activity
Specific Function
Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is al...
Gene Name
PTGDR2
Uniprot ID
Q9Y5Y4
Uniprot Name
Prostaglandin D2 receptor 2
Molecular Weight
43267.15 Da
References
  1. Wright DH, Metters KM, Abramovitz M, Ford-Hutchinson AW: Characterization of the recombinant human prostanoid DP receptor and identification of L-644,698, a novel selective DP agonist. Br J Pharmacol. 1998 Apr;123(7):1317-24. [PubMed:9579725]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
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:10973807]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
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, a...
Gene Name
SLCO2A1
Uniprot ID
Q92959
Uniprot Name
Solute carrier organic anion transporter family member 2A1
Molecular Weight
70043.33 Da
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:8787677]
  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:7754369]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
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 an...
Gene Name
SLCO3A1
Uniprot ID
Q9UIG8
Uniprot Name
Solute carrier organic anion transporter family member 3A1
Molecular Weight
76552.135 Da
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:14631946]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 17:08