Beraprost (sodium salt)
(Synonyms: 贝前列素钠) 目录号 : GC42924
A stable, orally active analog of prostacyclin
Cas No.:88475-69-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Beraprost is an analog of prostacyclin in which the unstable enol-ether has been replaced by a benzofuran ether function. This modification increases the plasma half-life from 30 seconds to several hours, and permits the compound to be taken orally. Doses of 20-100 µg in humans, given 1 to 3 times per day, have been demonstrated to improve clinical end points in diseases responsive to prostacyclin. Oral beraprost therapy improved the survival and pulmonary hemodynamics of patients with primary pulmonary hypertension. Beraprost inhibits platelet aggregation in healthy subjects and in diabetic patients at similar doses.
| Cas No. | 88475-69-8 | SDF | |
| 别名 | 贝前列素钠 | ||
| Canonical SMILES | O[C@H]1C(/C=C/[C@@H](O)C(C)CC#CC)[C@@H](C(C=CC=C2CCCC([O-])=O)=C2O3)[C@@H]3C1.[Na+] | ||
| 分子式 | C24H29O5•Na | 分子量 | 420.5 |
| 溶解度 | DMF: 77 mg/ml,DMSO: 43 mg/ml,Ethanol: 20 mg/ml,PBS (pH 7.2): 19 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3781 mL | 11.8906 mL | 23.7812 mL |
| 5 mM | 0.4756 mL | 2.3781 mL | 4.7562 mL |
| 10 mM | 0.2378 mL | 1.1891 mL | 2.3781 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Prostacyclin among prostanoids
Pharmacol Rep 2008 Jan-Feb;60(1):3-11.PMID:18276980doi
Prostanoids are cyclic lipid mediators which arise from enzymic cyclooxygenation of linear polyunsaturated fatty acids, e.g. arachidonic acid (20:4 n 6, AA). Biologically active prostanoids deriving from AA include stable prostaglandins (PGs), e.g. PGE(2), PGF(2alpha), PGD(2), PGJ(2) as well as labile prostanoids, i.e. PG endoperoxides (PGG(2), PGH(2)), thromboxane A(2) (TXA(2)) and prostacyclin (PGI(2)). A "Rabbit aorta Contracting Substance" (RCS) played important role in discovering of labile PGs. RCS was discovered in the Vane's Cascade as a labile product released along with PGs from the activated lung or spleen. RCS was identified as a mixture of PG endoperoxides and thromboxane A(2). Stable PGs regulate the cell cycle, smooth muscle tone and various secretory functions; they also modulate inflammatory and immune reactions. PG endoperoxides are intermediates in biosynthesis of all prostanoids. Thromboxane A(2) (TXA(2)) is the most labile prostanoid (with a half life of 30 s at 37 degrees C). It is generated mainly by blood platelets. TXA(2) is endowed with powerful vasoconstrictor, cytotoxic and thrombogenic properties. Again the Vane's Cascade was behind the discovery of prostacyclin (PGI(2)) with a half life of 4 min at 37 degrees C. It is produced by the vascular wall (predominantly by the endothelium) and it acts as a physiological antagonist of TXA(2). Moreover, prostacyclin per se is a powerful cytoprotective agent that exerts its action through activation of adenylate cyclase, followed by an intracellular accumulation of cyclic-AMP in various types of cells. In that respect PGI(2) collaborates with the system consisting of NO synthase (eNOS)/nitric oxide free radical (NO)/guanylate cyclase/cyclic-GMP. Both cyclic nucleotides (c-AMP and c-GMP) act in synergy as two energetic fists which defend the cellular machinery from being destroyed by endogenous or exogenous aggressors. Recently, a new partner has been recognized in this endogenous defensive squadron, i.e. a system consisting of heme oxygenase (HO-1)/carbon monoxide (CO)/biliverdin/biliverdin reductase/bilirubin. The expanding knowledge on the pharmacological steering of this enzymic triad (PGI(2)-S/eNOS/HO-1) is likely to contribute to the rational therapy of many systemic diseases such as atherosclerosis, diabetes mellitus, arterial hypertension or Alzheimer diseases. The discovery of prostacyclin broadened our pathophysiological horizon, and by itself opened new therapeutic possibilities. Prostacyclin sodium salt and its synthetic stable analogues (iloprost, Beraprost, treprostinil, epoprostenol, cicaprost) are useful drugs for the treatment of the advanced critical limb ischemia, e.g. in the course of Buerger's disease, and also for the treatment of pulmonary artery hypertension (PAH). In this last case a synergism between prostacyclin analogues and sildenafil (a selective phosphodiesterase 5 inhibitor) or bosentan (an endothelin ET-1 receptor antagonist) points our to complex mechanisms controlling pulmonary circulation. At the Jagiellonian University we have demonstrated that several well recognised cardiovascular drugs, e.g. ACE inhibitors (ACE-I), statins, some of beta-adrenergic receptor antagonists, e.g. carvedilol or nebivolol, anti-platelet thienopyridines (ticlopidine, clopidogrel) and a metabolite of vitamin PP--N(1)-methyl-nicotinamide--all of them are endowed with the in vivo PGI(2)-releasing properties. In this way, the foundations for the Endothelial Pharmacology were laid.
Identification of Transporters Involved in Beraprost Sodium Transport In Vitro
Eur J Drug Metab Pharmacokinet 2017 Feb;42(1):117-128.PMID:26961540DOI:10.1007/s13318-016-0327-4.
Background and objective: Beraprost sodium (BPS) is a chemically stable and orally active prostacyclin analog that is used in the treatment of chronic arterial occlusive disease since 1992 and primary pulmonary hypertension since 1999 in Japan. Multiple-drug therapy is common in clinical practice, and BPS is co-administered with other drugs. Membrane transporters are known to markedly affect pharmacokinetics, safety and efficacy, and many transporter-based drug-drug interactions have been recently reported. However, information on the transporters involved in the pharmacokinetics of BPS is limited. Methods: First of all, we have examined 11 transporters, ABCB1 (P-glycoprotein: P-gp), ABCG2 (breast cancer resistance protein: BCRP), SLC22A6 (organic anion transporter 1: OAT1), SLC22A8 (organic anion transporter 3: OAT3), SLCO1B1 (organic anion transporting polypeptide 1B1: OATP1B1), SLCO1B3 (organic anion transporting polypeptide 1B3: OATP1B3), SLCO2B1 (organic anion transporting polypeptide 2B1: OATP2B1), SLC22A1 (organic cation transporter 1: OCT1), SLC22A2 (organic cation transporter 2: OCT2), ABCB11 (bile-salt export pump: BSEP), and ABCC2 (multidrug resistance associated protein 2: MRP2) to clarify which of them would be candidates that might recognize BPS as their substrate in transporter-expressing LLC-PK1, S2, and HEK293 cells as well as in membrane vesicles. Furthermore, we determined whether the transport of BPS was inhibited by the typical inhibitors of each transporter, i.e., verapamil for P-gp, Ko143 for BCRP, probenecid for OAT3, rifampicin for OATP1B1 and OATP1B3, cyclosporine for BSEP, and sulfobromophthalein (BSP) for MRP2. Results: The results obtained showed that P-gp, BCRP, OAT3, OATP1B1, OATP1B3, BSEP and MRP2 might be candidates for BPS transporters. From the further evaluation with the typical inhibitors of each transporter, it was confirmed that BPS is a substrate for P-gp, BCRP, OAT3, OATP1B1, OATP1B3 and MRP2, because the typical inhibitor, cyclosporine, had no effects on BPS transport by BSEP. Conclusions: BPS is a substrate of 6 transporters: P-gp, BCRP, OAT3, OATP1B1, OATP1B3, and MRP2, because their expressing cells and vesicles transported BPS more than in the controls, and BPS transport activities were reduced by the typical inhibitors of tested transporters. Although there are no reports regarding drug-drug interactions between BPS and possible combination drugs expected due to transporters, it may be necessary to notice that that substrates or inhibitors for the 6 mentioned transporters may have effects on pharmacokinetics of BPS when co-administered.
Prostanoids for pulmonary arterial hypertension
Am J Respir Med 2003;2(2):123-37.PMID:14720012DOI:10.1007/BF03256644.
Pulmonary arterial hypertension (PAH) is a severe condition that markedly reduces exercise capacity and survival in the affected patient population. PAH includes primary pulmonary hypertension (PPH) and pulmonary hypertension associated with collagen vascular diseases, congenital systemic-to-pulmonary shunts, portal hypertension and HIV infection. All these conditions share virtually identical obstructive pathologic changes of the pulmonary microcirculation and probably similar pathobiologic processes. The pathophysiology is characterized by a progressive increase in pulmonary vascular resistance, leading to right ventricular failure and death. Prostacyclin is an endogenous substance that is produced by vascular endothelial cells and induces vasodilatation, inhibition of platelet activity, and antiproliferative effects. A dysregulation of prostacyclin metabolic pathways has been shown in patients with PAH and this represents the rationale for the exogenous therapeutic administration of this substance. The clinical use of prostacyclin in patients with PAH has been made possible by the synthesis of stable analogs that possess different pharmacokinetic properties but share similar pharmacodynamic effects. Experience in humans has been initially collected with epoprostenol, which is a synthetic salt of prostacyclin. Epoprostenol has a short half-life in the circulation and requires continuous administration by the intravenous route by means of infusion pumps and permanent tunnelized catheters. In addition, epoprostenol is unstable at room temperature, and the complex delivery system required is associated with several adverse effects and potentially serious complications. For these reasons, alternatives to intravenous epoprostenol have been sought and this has led to the development of analogs that can be administered subcutaneously (treprostinil), orally (Beraprost sodium) or by inhalation (iloprost). Three unblinded clinical trials and several uncontrolled trials have shown that treatment with epoprostenol improved symptoms and exercise capacity in New York Heart Association (NYHA) class III and IV PAH patients and also survival in patients with PPH. Subcutaneous treprostinil improved symptoms, exercise, hemodynamics and clinical events in the largest clinical trial ever performed in PAH, but local infusion site reactions limited efficacy in a proportion of patients. Oral Beraprost sodium improved exercise capacity only in patients with PPH and is the only prostacyclin analog that has also been tested in NYHA class II patients. Inhaled iloprost has improved symptoms, exercise capacity and clinical events in patients with PAH and inoperable chronic thromboembolic pulmonary hypertension. The favorable effects of prostanoids observed in all studies coupled with different profiles of adverse events and tolerability for each prostacyclin analog allow the unique opportunity to select the most appropriate compound for the individual patient with PAH.
Effect of long-term administration of a prostacyclin analogue (Beraprost sodium) on myocardial fibrosis in Dahl rats
J Vet Med Sci 2007 Dec;69(12):1271-6.PMID:18176024DOI:10.1292/jvms.69.1271.
Beraprost sodium (BPS) is an orally active prostacyclin analogue. The effects of BPS on the heart, including coronary circulation improvement, myocardial and vascular protection and anti-fibrosis effect on myocardium interstitium, have previously been demonstrated. However, the effects of BPS on hemodynamics, cardiac function and myocardial contractility in patients in the hypertrophic phase have not been clarified. Therefore, in the present study, the effects of BPS under long-term administration were investigated using the hypertension model of salt-sensitive Dahl rats. Six-week-old Dahl rats were divided into three groups, an 8% high salt diet group treated with BPS (BPS group), an untreated 8% high salt diet group (HHF group) and an untreated 0.3% low salt diet group (Control group), and observations were conducted until 17 weeks of age. In the BPS and HHF groups, the survival rates after 11 weeks of high salt diet intake were 87.5% and 47.1%, respectively (p<0.05). At 17 weeks of age, the atrial systolic peak velocity/early diastolic peak velocity and heart weight index of the BPS group decreased significantly compared with the HHF group (p<0.05). The HHF group exhibited significantly more severe myocardial fibrosis mainly in the endocardial layer of the left and right ventricles compared with the BPS and Control groups (p<0.05). In the present study, long-term BPS administration preserved diastolic function and prevented myocardial interstitial fibrosis in the non-compensatory phase. The results of the present study suggest that BPS is effective for treatment of hypertensive cardiac hypertrophy.
PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation
Int J Mol Sci 2020 Jun 22;21(12):4433.PMID:32580367DOI:10.3390/ijms21124433.
Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of Beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria and renal injury in salt-loaded DS rats with elevated blood pressure, accompanied by renal inflammation suppression. Notably, high salt increased renal expression of active Rac1, followed by increased Sgk1 expressions, a downstream molecule of mineralocorticoid receptor (MR) signal, indicating salt-induced activation of Rac1-MR pathway. However, BPS administration inhibited salt-induced Rac1-MR activation as well as renal inflammation and damage, suggesting that Rac1-MR pathway is involved in anti-inflammatory and renoprotective effects of PGI2. Based upon Rac1 activated by inflammation, moreover, BPS inhibited salt-induced activation of Rac1-MR pathway by renal inflammation suppression, resulting in the attenuation of renal damage in salt-loaded DS rats. Thus, BPS is efficacious for the treatment of salt-induced renal injury.