General
Preferred name
EPOPROSTENOL
Synonyms
EPOPROSTENOL SODIUM ()
Flolan ()
U-53217A ()
Veletri ()
Prostacyclin sodium salt ()
Epoprostenolsodium ()
U-53,217A ()
Sodium prostacyclin ()
PGI2 ()
U-53217 ()
PGX ()
ACT-385781A ()
Prostaglandin X ()
PGI2 ()
U-53,217 ()
Prostaglandin I2 ()
PG-I2 ()
PROSTACYCLIN ()
Prostaglandin I2 (sodium salt) ()
P&D ID
PD014373
CAS
61849-14-7
35121-78-9
Tags
natural product
drug
available
Approved by
FDA
First approval
1995
Drug Status
approved
Drug indication
Inhibitor (platelet)
Pulmonary hypertension
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; the in vivo half-life of epoprostenol in humans is therefore expected to be no greater than 6 minutes.
PHARMACODYNAMICS
Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol.
INDICATION
For the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.
ROE
Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
TOXICITY
Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of epoprostenol. Single intravenous doses at 10 and 50 mg/kg (2703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
METABOLISM
Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
DESCRIPTION
PGI2 is an endogenous prostaglandin. Synthetic PGI2 is known as epoprostenol. PG12 activates prostanoid family GPCRs.
(GtoPdb)
MOA
Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor (prostacyclin receptor) is activated when it binds to PGI2. This activation, in turn, signals adenylyl cyclase to produce cAMP. cAMP goes on to inhibit any undue platelet activation (in order to promote circulation) and also counteracts any increase in cytosolic calcium levels which would result from thromboxane A2 (TXA2) binding (leading to platelet activation and subsequent coagulation). PGI2 also binds to endothelial prostacyclin receptors and in the same manner raise cAMP levels in the cytosol. This cAMP then goes on to activate protein kinase A (PKA). PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists.
MOA
Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI2) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A2 binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists.
DESCRIPTION
Epoprostenol Sodium is the sodium salt form of epoprostenol, which is a synthetic prostacyclin. It has vasodilatory and anticoagulant activity. It is a short-lived product of the cyclooxygenase pathway in vascular endothelial cells. It prevents the formation of platelet plugs and is an effective vasodilator. It is a potent inhibitor of platelet aggregation by antagonizing thromboxane A2 and stimulating platelet adenylyl cyclase. It directly simulates prostaglandin receptors in arterial vascular smooth muscle, thereby causing vasodilatation. lt is also used for the treatment of pulmonary hypertension. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is vasoprotective, protecting arterial walls from injury-induced lesions and cytoprotective in the liver and gastrointestinal tract. It was developed by GlaxoSmithKline and has been listed.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
3
Compound Sets
19
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
JUMP-Target 1 Compound Set
NCATS Inxight Approved Drugs
NPC Screening Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
59
Molecular Weight
352.22
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
3
Rotatable Bonds
10
Ring Count
2
Aromatic Ring Count
0
cLogP
3.41
TPSA
86.99
Fraction CSP3
0.75
Chiral centers
5.0
Largest ring
5.0
QED
0.41
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
P2RY12, PTGER1, PTGER4, PTGIR, PTGIS
PTGIS
Indication
hypertension
MOA
prostacyclin analog
Therapeutic Class
Antihypertensive Agents
Solubility
H2O: 1 mg/mL Hydrolyzes to 6-ketoprostaglandin F1α in aqueous solution
ethanol: soluble50 mg/mL
Source data
