Identification

Name
Beraprost
Accession Number
DB05229
Type
Small Molecule
Groups
Investigational
Description

Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
35E3NJJ4O6
CAS number
88430-50-6
Weight
Average: 420.4738
Monoisotopic: 420.191268713
Chemical Formula
C24H29NaO5
InChI Key
YTCZZXIRLARSET-VJRSQJMHSA-M
InChI
InChI=1S/C24H30O5.Na/c1-3-4-7-15(2)19(25)13-12-17-20(26)14-21-23(17)18-10-5-8-16(24(18)29-21)9-6-11-22(27)28;/h5,8,10,12-13,15,17,19-21,23,25-26H,6-7,9,11,14H2,1-2H3,(H,27,28);/q;+1/p-1/b13-12+;/t15?,17-,19+,20+,21-,23-;/m0./s1
IUPAC Name
sodium 4-[(2S,3R,4R,6S)-4-hydroxy-3-[(1E,3S)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl]-7-oxatricyclo[6.4.0.0²,⁶]dodeca-1(12),8,10-trien-9-yl]butanoate
SMILES
[Na+].[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)C(C)CC#CC)[C@@]1([H])C1=CC=CC(CCCC([O-])=O)=C1O2

Pharmacology

Indication

For the treatment of pulmonary hypertension.

Pharmacodynamics

Beraprost is a stable, orally active prostacyclin analogue with vasodilatory, antiplatelet and cytoprotective effects. Beraprost is generally well tolerated and appears to be an effective agent in the treatment of patients with Buerger's disease and arteriosclerosis obliterans. Comparative data from a large randomised trial indicated that the drug appears as effective as ticlopidine in patients with these conditions. In patients with intermittent claudication, significant benefits of beraprost compared with placebo were reported in a randomised clinical trial; however, the use of beraprost in these patients is not supported by recent preliminary unpublished data from a large, phase III, placebo-controlled study. Limited data suggest some efficacy with long-term beraprost treatment of patients with PAH, where options are few and where oral administration of the drug could be a considerable advantage over intravenous prostacyclin (PGI2) therapy.

Mechanism of action

Beraprost acts by binding to prostacyclin membrane receptors ultimately inhibiting the release of Ca2+ from intracellular storage sites. This reduction in the influx of Ca2+ has been postulated to cause relaxation of the smooth muscle cells and vasodilation.

TargetActionsOrganism
UProstacyclin receptorNot AvailableHuman
Absorption

Oral bioavailability is 50–70%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

35–40 minutes

Clearance
Not Available
Toxicity
Not Available
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 Beraprost 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 Beraprost is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Beraprost is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Beraprost can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Beraprost can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Beraprost is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Beraprost can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Beraprost can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Beraprost.
AbirateroneThe metabolism of Beraprost can be decreased when combined with Abiraterone.
Food Interactions
Not Available

References

General References
  1. Lin H, Lee JL, Hou HH, Chung CP, Hsu SP, Juan SH: Molecular mechanisms of the antiproliferative effect of beraprost, a prostacyclin agonist, in murine vascular smooth muscle cells. J Cell Physiol. 2008 Feb;214(2):434-41. [PubMed:17620284]
  2. Melian EB, Goa KL: Beraprost: a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs. 2002;62(1):107-33. [PubMed:11790158]
External Links
PubChem Compound
23663404
PubChem Substance
175426958
ChemSpider
5293168
ChEMBL
CHEMBL435883
Wikipedia
Beraprost
ATC Codes
B01AC19 — Beraprost
MSDS
Download (15.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Adult Males / Pharmacokinetics of TRK-100-STP1
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentRenal Insufficiency,Chronic1
4TerminatedPreventionType 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00811 mg/mLALOGPS
logP3.81ALOGPS
logP3.6ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)4.2ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area89.82 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity123.56 m3·mol-1ChemAxon
Polarizability44.85 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8736
Blood Brain Barrier+0.7754
Caco-2 permeable+0.5868
P-glycoprotein substrateSubstrate0.6165
P-glycoprotein inhibitor INon-inhibitor0.9641
P-glycoprotein inhibitor IINon-inhibitor0.9395
Renal organic cation transporterNon-inhibitor0.9342
CYP450 2C9 substrateNon-substrate0.7409
CYP450 2D6 substrateNon-substrate0.8255
CYP450 3A4 substrateNon-substrate0.5132
CYP450 1A2 substrateInhibitor0.5177
CYP450 2C9 inhibitorNon-inhibitor0.8578
CYP450 2D6 inhibitorNon-inhibitor0.8834
CYP450 2C19 inhibitorNon-inhibitor0.7827
CYP450 3A4 inhibitorInhibitor0.6633
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7365
Ames testAMES toxic0.5331
CarcinogenicityNon-carcinogens0.9445
BiodegradationNot ready biodegradable0.5301
Rat acute toxicity3.6575 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8871
hERG inhibition (predictor II)Non-inhibitor0.9611
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as coumarans. These are compounds containing the coumaran skeleton, which consists of a benzene ring fused to a 2,3-dihydrofuran ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Coumarans
Sub Class
Not Available
Direct Parent
Coumarans
Alternative Parents
Alkyl aryl ethers / Benzenoids / Secondary alcohols / Cyclic alcohols and derivatives / Carboxylic acid salts / Oxacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Organic zwitterions / Organic sodium salts
show 3 more
Substituents
Coumaran / Alkyl aryl ether / Benzenoid / Cyclic alcohol / Carboxylic acid salt / Secondary alcohol / Monocarboxylic acid or derivatives / Ether / Carboxylic acid / Carboxylic acid derivative
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Melian EB, Goa KL: Beraprost: a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs. 2002;62(1):107-33. [PubMed:11790158]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Fukazawa T, Yajima K, Miyamoto Y: Evaluation of drug-drug interaction potential of beraprost sodium mediated by P450 in vitro. Yakugaku Zasshi. 2008 Oct;128(10):1459-65. [PubMed:18827466]

Drug created on October 21, 2007 16:24 / Updated on November 02, 2018 06:09