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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
Structure for Iloprost (DB01088)
- 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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Nyha class iii pulmonary arterial hypertension •••••••••••• Management of Nyha class iv pulmonary arterial hypertension •••••••••••• Treatment of Severe frostbite •••••••••••• ••••• - Contraindications & Blackbox Warnings
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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
Target Actions Organism AProstacyclin receptor agonistHumans AProstaglandin E2 receptor EP2 subtype agonistHumans AProstaglandin E2 receptor EP1 subtype agonistHumans U3',5'-cyclic-AMP phosphodiesterase 4A inducerHumans U3',5'-cyclic-AMP phosphodiesterase 4B inducerHumans U3',5'-cyclic-AMP phosphodiesterase 4C inducerHumans U3',5'-cyclic-AMP phosphodiesterase 4D inducerHumans UTissue-type plasminogen activator other/unknownHumans UProstaglandin D2 receptor 2 agonistHumans - 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
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- 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Iloprost is combined with Abaloparatide. Abciximab Iloprost may increase the anticoagulant activities of Abciximab. Acebutolol Iloprost may increase the hypotensive activities of Acebutolol. Acenocoumarol Iloprost may increase the anticoagulant activities of Acenocoumarol. Acetylcholine Iloprost 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Iloprost tromethamine 807T91913V 697225-02-8 KZSSWXACMCYLBM-RMWNCEGRSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aurlumyn Injection, solution 100 ug/1mL Intravenous Eicos Sciences Inc. 2024-05-01 Not applicable US 
Ventavis Solution 10 μg/ml Respiratory (inhalation) Bayer Ag 2016-09-08 Not applicable EU 
Ventavis Solution 10 ?g/ml Respiratory (inhalation) Bayer Ag 2021-03-03 Not applicable EU Ventavis Solution 10 ug/1mL Respiratory (inhalation) CoTherix, Inc. 2006-05-10 2006-05-10 US Ventavis Solution 10 μg/ml Respiratory (inhalation) Bayer Ag 2016-09-08 Not applicable EU
Categories
- ATC Codes
- B01AC11 — Iloprost
- Drug Categories
- Agents Causing Muscle Toxicity
- Antiplatelet agents
- Autacoids
- Biological Factors
- Blood and Blood Forming Organs
- Cardiovascular Agents
- Eicosanoids
- Fatty Acids
- Fatty Acids, Unsaturated
- Hematologic Agents
- Hypotensive Agents
- Inflammation Mediators
- Lipids
- OATP2B1/SLCO2B1 substrates
- Platelet Aggregation Inhibitors Excl. Heparin
- Prostacyclin Analogues
- Prostaglandins
- Prostaglandins, Synthetic
- Vasodilating Agents
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: VENTAVIS (iloprost) inhalation solution, for oral inhalation use (March 2022) [Link]
- FDA Approved Drug Products: AURLUMYN (iloprost) injection, for intravenous use (February 2024) [Link]
- Cayman Chemical: Iloprost MSDS [Link]
- External Links
- PubChem Compound
- 5311181
- PubChem Substance
- 46507818
- ChemSpider
- 4470703
- BindingDB
- 23954
- 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 Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Chronic Obstructive Pulmonary Disease (COPD) / Video-assisted Thoracoscopic Surgery (VATS) 1 somestatus stop reason just information to hide Not Available Completed Not Available Hypertension, Essential Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Peripheral Arterial Disease (PAD) 1 somestatus stop reason just information to hide Not Available Completed Not Available Pulmonary Arterial Hypertension (PAH) 5 somestatus stop reason just information to hide Not Available Completed Not Available Pulmonary Hypertension (PH) 8 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Actelion Pharmaceuticals Inc.
- Berlimed Sa
- Cotherix Inc.
- Dosage Forms
Form Route Strength Injection, solution Intravenous 100 ug/1mL Injection Intravenous Injection, solution, concentrate Cutaneous; Intravenous 0.05 MG/0.5ML Injection, solution, concentrate Intravenous Injection, solution, concentrate Intravenous 0.05 MG/0.5ML Injection, solution, concentrate Intravenous 0100 MG/1ML Injection Intravenous 50 mcg Concentrate Intravenous Injection, solution Intravenous 20 mcg/ml Injection, solution, concentrate Intravenous 50 mcg/0.5ml Solution Respiratory (inhalation) Solution Respiratory (inhalation) 20 MICROGRAMMI/ML Solution Respiratory (inhalation) 10 Mikrogramm/ml Injection, solution, concentrate Intravenous 20 Mikrogramm/ml Solution Respiratory (inhalation) 20 Mikrogramm/ml Injection, solution, concentrate Intravenous 100 MICROGRAMMI/ML Injection, solution Intravenous 20 mcg/2ml Injection, solution Intravenous Aerosol Respiratory (inhalation) 10 MCG/ML Solution Respiratory (inhalation) 0.01 mg/1mL Solution Respiratory (inhalation) 0.013 mg Solution Respiratory (inhalation) 0.02 mg/1mL Solution Respiratory (inhalation) 10 ug/1mL Solution Respiratory (inhalation) 10 ?g/ml Solution Respiratory (inhalation) 10 μg/ml Solution Respiratory (inhalation) 20 MCG/ML Solution Respiratory (inhalation) 20 μg/ml Solution Respiratory (inhalation) 20 ?g/ml Solution Respiratory (inhalation) 20 mcg Solution Respiratory (inhalation) 2000000 mcg Solution Respiratory (inhalation) 10 mcg/ml Solution Nasal 0.010 mg/ml Solution Respiratory (inhalation) 20 cg Aerosol Respiratory (inhalation) 0.01 mg/1ml - Prices
Unit description Cost Unit Ventavis 10 mcg/1 ml solution 74.4USD ml Ventavis 20 mcg/1 ml solution 74.4USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) -98 https://cdn.caymanchem.com/cdn/msds/18215m.pdf boiling point (°C) 57 https://cdn.caymanchem.com/cdn/msds/18215m.pdf water solubility 330 g/L https://cdn.caymanchem.com/cdn/msds/18215m.pdf logP 4.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00874 mg/mL ALOGPS logP 4.22 ALOGPS logP 3.56 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 4.66 Chemaxon pKa (Strongest Basic) -0.87 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 77.76 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 105.18 m3·mol-1 Chemaxon Polarizability 42.68 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9543 Blood Brain Barrier + 0.5506 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.7459 P-glycoprotein inhibitor I Non-inhibitor 0.6507 P-glycoprotein inhibitor II Non-inhibitor 0.8227 Renal organic cation transporter Non-inhibitor 0.8698 CYP450 2C9 substrate Non-substrate 0.8526 CYP450 2D6 substrate Non-substrate 0.8946 CYP450 3A4 substrate Substrate 0.6553 CYP450 1A2 substrate Non-inhibitor 0.5515 CYP450 2C9 inhibitor Non-inhibitor 0.7963 CYP450 2D6 inhibitor Non-inhibitor 0.8072 CYP450 2C19 inhibitor Non-inhibitor 0.719 CYP450 3A4 inhibitor Inhibitor 0.5377 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7556 Ames test Non AMES toxic 0.7104 Carcinogenicity Non-carcinogens 0.9587 Biodegradation Not ready biodegradable 0.6052 Rat acute toxicity 2.7260 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9288 hERG inhibition (predictor II) Non-inhibitor 0.6964
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0029000000-31b136be94039d233232 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0009000000-3d97279dd73ca80d8993 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-052f-1169000000-95bcd53b77c6621a63f0 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-1298000000-c14f4b9c28e606770fca Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0bt9-2169000000-c1dfe93cc6985f9524ff Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0fri-9740000000-e45bbe51efc93c8930c7 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 194.31767 predictedDeepCCS 1.0 (2019) [M+H]+ 196.87813 predictedDeepCCS 1.0 (2019) [M+Na]+ 204.19557 predictedDeepCCS 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
- 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]
- 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]
- 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]
- 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]
- Tsai AL, Vijjeswarapu H, Wu KK: Interaction between platelet receptor and iloprost isomers. Biochim Biophys Acta. 1988 Jul 21;942(2):220-6. [Article]
- 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]
- 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]
- 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]
- 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
- 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
- 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]
- 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
- 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]
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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]
- 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
- 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
- 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
- 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
- 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]
- 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
- 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