BERAPROST

Details

Stereochemistry	EPIMERIC
Molecular Formula	C24H30O5
Molecular Weight	398.492
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 6
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)C(C)CC#CC)[C@@]1([H])C3=C(O2)C(CCCC(O)=O)=CC=C3

InChI

InChIKey=CTPOHARTNNSRSR-APJZLKAGSA-N

InChI=1S/C24H30O5/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)/b13-12+/t15?,17-,19+,20+,21-,23-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11790158
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26686607 | https://www.ncbi.nlm.nih.gov/pubmed/2665758 | http://www.astellas.co.id/product/view/4/5

Beraprost is a stable, orally active prostacyclin analogue. 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. Beraprost is indicated for the treatment of pulmonary hypertension and improvement of ulcers, pain & feeling of coldness associated with chronic arterial occlusion. In addition beraprost displays thyroid hormone receptor antagonistic properties.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Prostanoid IP receptor 18 Target ID: CHEMBL1995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2665758 \| https://www.ncbi.nlm.nih.gov/pubmed/10508233	Agonist 2678	133.0 nM [Kd]
Prostacyclin receptor 9 Target ID: P43252 Gene ID: 19222.0 Gene Symbol: Ptgir Target Organism: Mus musculus (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10508233	Agonist 2678	16.0 nM [Ki]
Prostanoid EP3 receptor 11 Target ID: CHEMBL4336 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10508233	Agonist 2678	110.0 nM [Ki]
Thyroid hormone receptor 6 Target ID: CHEMBL2111462 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26686607	Antagonist 2778	63.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary pulmonary hypertension 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11790158	Primary		Approved 8429	DORNER Approved Use Improvement of ulcers, pain & feeling of coldness associated with chronic arterial occlusion. Primary pulmonary Hypertension.
Chronic arterial occlusion 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11790158	Primary		Approved 8429	DORNER Approved Use Improvement of ulcers, pain & feeling of coldness associated with chronic arterial occlusion. Primary pulmonary Hypertension.

PubMed

Title	Date	PubMed
Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs.	1990 Jan	2110014
Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.	1995 Feb	7596955
Effect of beraprost sodium, a stable prostacyclin analogue, on pulmonary thromboembolism in mice.	1995 Jan 15	7740511
A dose-effect study of beraprost sodium in intermittent claudication.	1996 Jun	8761844
Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells.	1997 Sep	9313928
Prostacyclin analog prevents stress-induced expression of immediate early genes and gastric mucosal lesions in the rat stomach.	1999	10353594
Comparative effects of beraprost, a stable analogue of prostacyclin, with PGE(1), nitroglycerin and nifedipine on canine model of vasoconstrictive pulmonary hypertension.	2001 Mar	11334556
Beraprost: a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension.	2002	11790158
Amelioration by beraprost sodium, a prostacyclin analogue, of established renal dysfunction in rat glomerulonephritis model.	2002 Aug 2	12163121
Beraprost sodium-induced hypotension in two patients after cardiac surgery.	2006 Mar	16607058
Adaptive HNE-Nrf2-HO-1 pathway against oxidative stress is associated with acute gastric mucosal lesions.	2008 Sep	18617559
Efficacy of oral sildenafil in a beraprost-treated patient with severe pulmonary hypertension secondary to type I glycogen storage disease.	2009 Oct	19179780

Patents

Sample Use Guides

In Vivo Use Guide

Improvement of ulcers, pain & feeling of coldness associated with chronic arterial occlusion, Adult : 120 mcg daily in 3 divided doses. Primary pulmonary Hypertension: 60 mcg daily in 3 divided doses. Gradually increase dose if needed, up to a max of 180 mcg daily in 3-4 divided doses.

Route of Administration: Oral

In Vitro Use Guide

In suppressing platelet aggregation beraprost was especially potent with IC50 of 0.2-0.5 nM when platelets were activated by U46619, a thromboxane A2 analogue, or low concentrations of collagen which activates platelets through thromboxane A2 production. The IC50 values were 2-5 nM with ADP and epinephrine, which induce the formation of small aggregates independently of thromboxane A2 production.

Name

Type

Language

BERAPROST

Official Name

English

RAC-4-((1R,2R,3AS,8BS)-2-HYDROXY-1-((1E,3S,4RS)-3-HYDROXY-4-METHYLOCT-1-EN-6-YNYL)-2,3,3A,8B-TETRAHYDRO-1H-CYCLOPENTA(B)(1)BENZOFURAN-5-YL)BUTANOIC ACID

Common Name

English

(±)-(1R,2R,3AS,8BS)-2,3,3A,8B-TETRAHYDRO-2-HYDROXY-1-((E)-(3S,4RS)-3-HYDROXY-4-METHYL-1-OCTEN-6-YNYL)-1H-CYCLOPENTA(B)BENZOFURAN-5-BUTYRIC ACID

Common Name

English

beraprost [INN]

Common Name

English

1H-CYCLOPENTA(B)BENZOFURAN-5-BUTANOIC ACID, 2,3,3A,8B-TETRAHYDRO-2-HYDROXY-1-(3-HYDROXY-4-METHYL-1-OCTEN-6-YNYL)-

Common Name

English

TRK-100STP FREE ACID

Code

English

Beraprost [WHO-DD]

Common Name

English

MDL-201229

Code

English

BERAPROST [USAN]

Common Name

English

BERAPROST [MI]

Common Name

English

ML-1229

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

123099