Iloprost

Identification

Summary

Iloprost is a synthetic prostacyclin analog used to treat pulmonary arterial hypertension (PAH) and frostbites.

Brand Names
Aurlumyn, Ventavis
Generic Name
Iloprost
DrugBank Accession Number
DB01088
Background

Iloprost is an analog of prostacyclin (PGI2; epoprostenol), an endogenous prostanoid mainly produced in the vascular endothelium. It is more stable than prostacyclin, which is short-lived.4 Iloprost consists of a mixture of the 4R and 4S diastereoisomers at a ratio of approximately 53:47.6 It is a potent vasodilator with reported anti-thrombotic properties.2 Iloprost is available as an inhaled solution and intravenous formulations. It is used to treat pulmonary arterial hypertension (PAH) 6 and frostbites.7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 360.494
Monoisotopic: 360.23005951
Chemical Formula
C22H32O4
Synonyms
  • (5E)-[3aS,4R,5R,6aS)-5-Hydroxy-4-[(1E)-(3S,4RS)-3-hydroxy-4-methyloct-1-en-6-ynyl]-hexahydropentalen-2(1H)-ylidene]pentanoic acid
  • (E)-(3aS, 4R, 5R, 6aS)-hexahydro-5-hydroxy-4-[(E)-(3S,4RS)­ 3-hydroxy-4-methyl-1-octen-6-ynyl]-Δ2(1H),Δ-pentalenevaleric acid
  • Iloprost
  • PENTANOIC ACID, 5-((3AS,4R,5R,6AS)-HEXAHYDRO-5-HYDROXY-4-((1E,3S)-3-HYDROXY-4-METHYL-1-OCTEN-6-YNYL)-2(1H)-PENTALENYLIDENE)-, (5E)-
External IDs
  • ZK 00036374
  • ZK-00036374
  • ZK-36374

Pharmacology

Indication

Inhaled iloprost solution is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue diseases (23%).6

Intravenous iloprost is indicated for the treatment of severe frostbite in adults to reduce the risk of digit amputations. Effectiveness was established in young, healthy adults who suffered frostbite at high altitudes.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofNyha class iii pulmonary arterial hypertension••••••••••••
Management ofNyha class iv pulmonary arterial hypertension••••••••••••
Treatment ofSevere frostbite•••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer.6 In patients with primary pulmonary hypertension, iloprost decreased pulmonary vascular resistance and pulmonary artery pressure.1 Iloprost was shown to inhibit platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated.6

Iloprost is reported to attenuate ischemia-induced tissue injury. When administered intravenously in patients with peripheral vascular conditions such as critical leg ischemia and delayed amputation, iloprost was shown to promote cytoprotection.4,5 In isolated animal heart preparations and in intact animals with ischemia-reperfusion injury, preserved myocardial function was observed following iloprost administraion.4

Mechanism of action

In pulmonary arterial hypertension, endothelial vasoactive mediators such as nitric oxide and prostacyclin are released to induce vasoconstriction.2 Iloprost mimics the biological actions of prostacyclin, a short-lived prostanoid and potent vasodilator mainly produced in the vascular endothelium.4

The exact mechanism of iloprost in cytoprotection has not been fully elucidated; however, it is proposed that iloprost decreases catecholamine outflow from sympathetic nerve terminals, preserves mitochondrial function, and reduces oxidative stress. Decreased neutrophil accumulation and membrane stabilization have also been suggested.4

TargetActionsOrganism
AProstacyclin receptor
agonist
Humans
AProstaglandin E2 receptor EP2 subtype
agonist
Humans
AProstaglandin E2 receptor EP1 subtype
agonist
Humans
U3',5'-cyclic-AMP phosphodiesterase 4A
inducer
Humans
U3',5'-cyclic-AMP phosphodiesterase 4B
inducer
Humans
U3',5'-cyclic-AMP phosphodiesterase 4C
inducer
Humans
U3',5'-cyclic-AMP phosphodiesterase 4D
inducer
Humans
UTissue-type plasminogen activator
other/unknown
Humans
UProstaglandin D2 receptor 2
agonist
Humans
Absorption

Following inhalation of iloprost (5 mcg) patients with pulmonary hypertension have iloprost peak plasma levels of approximately 150 pg/mL. Iloprost was generally not detectable in plasma 30 minutes to one hour after inhalation. The absolute bioavailability of inhaled iloprost has not been determined.6

When iloprost was administered via intravenous infusion at a rate of 2 ng/kg/min, steady-state plasma concentrations were 85 ng/L.4

Volume of distribution

Following intravenous infusion, the apparent steady-state volume of distribution was 0.7 to 0.8 L/kg in healthy subjects.6

Protein binding

Iloprost is approximately 60% protein-bound, mainly to albumin, and this ratio is concentration-independent in the range of 30 to 3000 pg/mL.6

Metabolism

In vitro studies reveal that cytochrome P450-dependent metabolism plays only a minor role in the biotransformation of iloprost. Iloprost is metabolized principally via β-oxidation of the carboxyl side chain. The main metabolite is tetranor-iloprost, which was shown to be pharmacologically inactive in animal experiments.4,6 In rabbits, dinor-iloprost has also been identified as a drug metabolite.3,4

Hover over products below to view reaction partners

Route of elimination

Unchanged iloprost and its metabolites are mainly excreted in urine.6 About 70% of the drug and metabolites undergo renal excretion. Following the administration of intravenous infusion at the rate of 2 ng/kg/min and oral dose at 0.1 ug/kg, fecal excretion was 12% and 17%, respectively.4

Half-life

The half-life of iloprost is 20 to 30 minutes.6

Clearance

Clearance in normal subjects was approximately 20 mL/min/kg.6

Adverse Effects
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Toxicity

The oral LD50 in rats is >100 mg/kg.8

Cases of overdose have been reported. Frequently observed symptoms following overdose are dizziness, headache, flushing, nausea, jaw pain or back pain. Hypotension, vomiting, and diarrhea are possible. A specific antidote is not known. Interruption of the inhalation session, monitoring, and symptomatic measures are recommended.6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe risk or severity of adverse effects can be increased when Iloprost is combined with Abaloparatide.
AbciximabIloprost may increase the anticoagulant activities of Abciximab.
AcebutololIloprost may increase the hypotensive activities of Acebutolol.
AcenocoumarolIloprost may increase the anticoagulant activities of Acenocoumarol.
AcetylcholineIloprost may increase the hypotensive activities of Acetylcholine.
Food Interactions
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Taking iloprost with anticoagulant/antiplatelet herbs may increase the risk of bleeding occurring as an adverse effect. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Iloprost tromethamine807T91913V697225-02-8KZSSWXACMCYLBM-RMWNCEGRSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AurlumynInjection, solution100 ug/1mLIntravenousEicos Sciences Inc.2024-05-01Not applicableUS flag
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2016-09-08Not applicableEU flag
VentavisSolution0.01 mg/1mLRespiratory (inhalation)Actelion Pharmaceuticals US, Inc.2005-05-07Not applicableUS flag
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2016-09-08Not applicableEU flag
VentavisSolution10 μg/mlRespiratory (inhalation)Bayer Ag2016-09-08Not applicableEU flag

Categories

ATC Codes
B01AC11 — Iloprost
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Aliphatic homopolycyclic compound / Bicyclic monoterpenoid / Branched fatty acid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclic alcohol / Fatty alcohol / Hydrocarbon derivative
show 10 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
monocarboxylic acid, secondary alcohol, carbobicyclic compound (CHEBI:63916)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
JED5K35YGL
CAS number
78919-13-8
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

References

General References
  1. Olschewski H, Rohde B, Behr J, Ewert R, Gessler T, Ghofrani HA, Schmehl T: Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest. 2003 Oct;124(4):1294-304. doi: 10.1378/chest.124.4.1294. [Article]
  2. John J, Palevsky H: Clinical pharmacology and efficacy of inhaled iloprost for the treatment of pulmonary arterial hypertension. Expert Rev Clin Pharmacol. 2011 Mar;4(2):197-205. doi: 10.1586/ecp.10.136. [Article]
  3. Schermuly RT, Schulz A, Ghofrani HA, Meidow A, Rose F, Roehl A, Weissmann N, Hildebrand M, Kurz J, Grimminger F, Walmrath D, Seeger W: Pharmacokinetics and metabolism of infused versus inhaled iloprost in isolated rabbit lungs. J Pharmacol Exp Ther. 2002 Nov;303(2):741-5. doi: 10.1124/jpet.303.2.741. [Article]
  4. Grant SM, Goa KL: Iloprost. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. Drugs. 1992 Jun;43(6):889-924. doi: 10.2165/00003495-199243060-00008. [Article]
  5. Crooks S, Shaw BH, Andruchow JE, Lee CH, Walker I: Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study. CJEM. 2022 Sep;24(6):622-629. doi: 10.1007/s43678-022-00342-9. Epub 2022 Jul 23. [Article]
  6. FDA Approved Drug Products: VENTAVIS (iloprost) inhalation solution, for oral inhalation use (March 2022) [Link]
  7. FDA Approved Drug Products: AURLUMYN (iloprost) injection, for intravenous use (February 2024) [Link]
  8. Cayman Chemical: Iloprost MSDS [Link]
PubChem Compound
5311181
PubChem Substance
46507818
ChemSpider
4470703
BindingDB
23954
RxNav
40138
ChEBI
63916
ChEMBL
CHEMBL494
Therapeutic Targets Database
DAP000273
PharmGKB
PA164746843
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Iloprost

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableChronic Obstructive Pulmonary Disease (COPD) / Video-assisted Thoracoscopic Surgery (VATS)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableHypertension, Essential Hypertension1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailablePeripheral Arterial Disease (PAD)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailablePulmonary Arterial Hypertension (PAH)5somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailablePulmonary Hypertension (PH)8somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actelion Pharmaceuticals Inc.
  • Berlimed Sa
  • Cotherix Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous100 ug/1mL
InjectionIntravenous
Injection, solution, concentrateCutaneous; Intravenous0.05 MG/0.5ML
Injection, solution, concentrateIntravenous
Injection, solution, concentrateIntravenous0.05 MG/0.5ML
Injection, solution, concentrateIntravenous0100 MG/1ML
InjectionIntravenous50 mcg
ConcentrateIntravenous
Injection, solutionIntravenous20 mcg/ml
Injection, solution, concentrateIntravenous50 mcg/0.5ml
SolutionRespiratory (inhalation)
SolutionRespiratory (inhalation)20 MICROGRAMMI/ML
SolutionRespiratory (inhalation)10 Mikrogramm/ml
Injection, solution, concentrateIntravenous20 Mikrogramm/ml
SolutionRespiratory (inhalation)20 Mikrogramm/ml
Injection, solution, concentrateIntravenous100 MICROGRAMMI/ML
Injection, solutionIntravenous20 mcg/2ml
Injection, solutionIntravenous
AerosolRespiratory (inhalation)10 MCG/ML
SolutionRespiratory (inhalation)0.01 mg/1mL
SolutionRespiratory (inhalation)0.013 mg
SolutionRespiratory (inhalation)0.02 mg/1mL
SolutionRespiratory (inhalation)10 μg/ml
SolutionRespiratory (inhalation)10 ug/1mL
SolutionRespiratory (inhalation)10 ?g/ml
SolutionRespiratory (inhalation)20 MCG/ML
SolutionRespiratory (inhalation)20 ?g/ml
SolutionRespiratory (inhalation)20 μg/ml
SolutionRespiratory (inhalation)20 mcg
SolutionRespiratory (inhalation)2000000 mcg
SolutionRespiratory (inhalation)10 mcg/ml
SolutionNasal0.010 mg/ml
SolutionRespiratory (inhalation)20 cg
AerosolRespiratory (inhalation)0.01 mg/1ml
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
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)-98https://cdn.caymanchem.com/cdn/msds/18215m.pdf
boiling point (°C)57https://cdn.caymanchem.com/cdn/msds/18215m.pdf
water solubility330 g/Lhttps://cdn.caymanchem.com/cdn/msds/18215m.pdf
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/MSsplash10-004i-0029000000-31b136be94039d233232
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-3d97279dd73ca80d8993
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-1169000000-95bcd53b77c6621a63f0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-1298000000-c14f4b9c28e606770fca
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0bt9-2169000000-c1dfe93cc6985f9524ff
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fri-9740000000-e45bbe51efc93c8930c7
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-194.31767
predicted
DeepCCS 1.0 (2019)
[M+H]+196.87813
predicted
DeepCCS 1.0 (2019)
[M+Na]+204.19557
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase
Specific Function
guanyl-nucleotide exchange factor activity
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Tsai AL, Vijjeswarapu H, Wu KK: Interaction between platelet receptor and iloprost isomers. Biochim Biophys Acta. 1988 Jul 21;942(2):220-6. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle
Specific Function
prostaglandin E receptor activity
Gene Name
PTGER2
Uniprot ID
P43116
Uniprot Name
Prostaglandin E2 receptor EP2 subtype
Molecular Weight
39759.945 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General 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 important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues
Specific Function
D1 dopamine receptor binding
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4A
Uniprot ID
P27815
Uniprot Name
3',5'-cyclic-AMP 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:15260978). May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4B
Uniprot ID
Q07343
Uniprot Name
3',5'-cyclic-AMP 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4C
Uniprot ID
Q08493
Uniprot Name
3',5'-cyclic-AMP 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4D
Uniprot ID
Q08499
Uniprot Name
3',5'-cyclic-AMP 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other/unknown
General 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 tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy (By similarity)
Specific Function
phosphoprotein binding
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General 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 also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses
Specific Function
G protein-coupled receptor activity
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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: VENTAVIS (iloprost) inhalation solution, for oral inhalation use (March 2022) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76697.93 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane (PubMed:11997326, PubMed:26692285, PubMed:8787677). PGs and thromboxanes play fundamental roles in diverse functions such as intraocular pressure, gastric acid secretion, renal salt and water transport, vascular tone, and fever (PubMed:15044627). Plays a role in the clearance of PGs from the circulation through cellular uptake, which allows cytoplasmic oxidation and PG signal termination (PubMed:8787677). PG uptake is dependent upon membrane potential and involves exchange of a monovalent anionic substrate (PGs exist physiologically as an anionic monovalent form) with a stoichiometry of 1:1 for divalent anions or of 1:2 for monovalent anions (PubMed:29204966). Uses lactate, generated by glycolysis, as a counter-substrate to mediate PGE2 influx and efflux (PubMed:11997326). Under nonglycolytic conditions, metabolites other than lactate might serve as counter-substrates (PubMed:11997326). Although the mechanism is not clear, this transporter can function in bidirectional mode (PubMed:29204966). When apically expressed in epithelial cells, it facilitates transcellular transport (also called vectorial release), extracting PG from the apical medium and facilitating transport across the cell toward the basolateral side, whereupon the PG exits the cell by simple diffusion (By similarity). In the renal collecting duct, regulates renal Na+ balance by removing PGE2 from apical medium (PGE2 EP4 receptor is likely localized to the luminal/apical membrane and stimulates Na+ resorption) and transporting it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors inhibit Na+ resorption) (By similarity). Plays a role in endometrium during decidualization, increasing uptake of PGs by decidual cells (PubMed:16339169). Involved in critical events for ovulation (PubMed:27169804). Regulates extracellular PGE2 concentration for follicular development in the ovaries (By similarity). Expressed intracellularly, may contribute to vesicular uptake of newly synthesized intracellular PGs, thereby facilitating exocytotic secretion of PGs without being metabolized (By similarity). Essential core component of the major type of large-conductance anion channel, Maxi-Cl, which plays essential roles in inorganic anion transport, cell volume regulation and release of ATP and glutamate not only in physiological processes but also in pathological processes (By similarity). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
lipid transporter activity
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Putative organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormone L-thyroxine, prostanoids such as prostaglandin E1 and E2, bile acids such as taurocholate, glycolate and glycochenodeoxycholate and peptide hormones such as L-arginine vasopressin, likely operating in a tissue-specific manner (PubMed:10873595, PubMed:14631946, PubMed:16971491, PubMed:19129463, PubMed:30063921). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable)
Specific Function
organic anion transmembrane transporter activity
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:23