Eprodisate
(Synonyms: 伊罗地塞) 目录号 : GC35999
Eprodisate 伊罗地塞是一种新化合物，旨在干扰促淀粉样蛋白和糖胺聚糖之间的相互作用，从而抑制淀粉样蛋白原纤维的聚合和原纤维在组织中的沉积。Eprodisate 伊罗地塞减缓 AA 淀粉样变性相关肾病的进展，并且可能适用于其他类型的淀粉样变性。
Cas No.:21668-77-9
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
Eprodisate is a new compound designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues[1]. Eprodisate slow the progression of AA amyloidosis-related renal disease and has possible applicability to other types of amyloidosis[2].
[1]. Dember LM, et al. Eprodisate for the treatment of renal disease in AA amyloidosis. N Engl J Med. 2007 Jun 7;356(23):2349-60. [2]. Manenti L, et al. Eprodisate in amyloid A amyloidosis: a novel therapeutic approach• Expert Opin Pharmacother. 2008 Aug;9(12):2175-80.
| Cas No. | 21668-77-9 | SDF | |
| 别名 | 伊罗地塞 | ||
| Canonical SMILES | O=S(CCCS(=O)(O)=O)(O)=O | ||
| 分子式 | C3H8O6S2 | 分子量 | 204.22 |
| 溶解度 | DMSO: ≥ 125 mg/mL (612.09 mM) | 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 | 4.8967 mL | 24.4834 mL | 48.9668 mL |
| 5 mM | 0.9793 mL | 4.8967 mL | 9.7934 mL |
| 10 mM | 0.4897 mL | 2.4483 mL | 4.8967 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。
Eprodisate in amyloid A amyloidosis: a novel therapeutic approach?
Expert Opin Pharmacother 2008 Aug;9(12):2175-80.PMID:18671471DOI:10.1517/14656566.9.12.2175.
Background: Amyloid A (AA) amyloidosis can complicate chronic inflammatory diseases, chronic infections and recurrent periodic fever syndromes. Its treatment is challenging, given its heterogeneous spectrum of etiologies. Objective: To review the available literature regarding treatment options for AA amyloidosis, particularly focusing on Eprodisate, a newly developed inhibitor of fibrillogenesis. Methods: A PubMed search was performed without any date limits, mainly using the search terms 'amyloidosis', 'colchicine', 'Eprodisate', '1,3-propanedisulfonate', 'NC-503', 'Fibrillex' and 'TNF-blockers'. Results/conclusion: Antibiotics and colchicine are effective in preventing and treating infection-related and familial Mediterranean fever-related AA amyloidosis, respectively. Recently, TNF-alpha blockers have emerged as effective agents in inflammatory AA amyloidosis. Eprodisate binds to the glycosaminoglycan binding site on amyloid fibrils, thus targeting amyloid fibril polymerization and tissue deposition. Eprodisate has possible applicability to other types of amyloidosis; the results of a recent randomized trial showed that it may slow the progression of AA amyloidosis-related renal disease but confirmatory studies are necessary.
Eprodisate for the treatment of renal disease in AA amyloidosis
N Engl J Med 2007 Jun 7;356(23):2349-60.PMID:17554116DOI:10.1056/NEJMoa065644.
Background: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues. Methods: We performed a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of Eprodisate in patients with AA amyloidosis and kidney involvement. We randomly assigned 183 patients from 27 centers to receive Eprodisate or placebo for 24 months. The primary composite end point was an assessment of renal function or death. Disease was classified as worsened if any one of the following occurred: doubling of the serum creatinine level, reduction in creatinine clearance by 50% or more, progression to end-stage renal disease, or death. Results: At 24 months, disease was worsened in 24 of 89 patients who received Eprodisate (27%) and 38 of 94 patients given placebo (40%, P=0.06); the hazard ratio for worsening disease with Eprodisate treatment was 0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m(2) of body-surface area per year in the Eprodisate and the placebo groups, respectively (P=0.02). The drug had no significant effect on progression to end-stage renal disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95; P=0.94). The incidence of adverse events was similar in the two groups. Conclusions: Eprodisate slows the decline of renal function in AA amyloidosis. (ClinicalTrials.gov number, NCT00035334.)
Review of Eprodisate for the treatment of renal disease in AA amyloidosis
Int J Nephrol Renovasc Dis 2012;5:37-43.PMID:22427728DOI:10.2147/IJNRD.S19165.
Secondary (AA) amyloidosis is a multisystem disorder complicating chronic infections or inflammatory diseases. It is characterized by extracellular deposit of fibrils composed of fragments of serum amyloid A (SAA), an acute phase reactant protein. The kidney is the most frequent organ involved, manifesting as progressive proteinuria and renal impairment. Attenuation of the level of circulating SAA protein by treating the underlying inflammatory condition remains the primary strategy in treating AA amyloidosis. However, at times, achieving adequate control of protein production can prove difficult. In addition, relapse of renal function often occurs rapidly following any subsequent inflammatory stimulus in patients with existing amyloidosis. Recently there has been an interest in finding other potential strategies targeting amyloid deposits themselves. Eprodisate is a sulfonated molecule with a structure similar to heparan sulfate. It competitively binds to the glycosaminoglycan-binding sites on SAA and inhibits fibril polymerization and amyloid deposition. Recent randomized clinical trial showed that it may slow down progressive renal failure in patients with AA amyloidosis. However confirmatory studies are needed and results of a second Phase III study are eagerly awaited to clarify whether or not Eprodisate has a place in treating renal amyloid disease.
[Amyloidosis in rheumatic diseases]
Ann Acad Med Stetin 2010;56 Suppl 1:7-15.PMID:21365934doi
Amyloidoses represent an inhomogeneous group of diseases characterized by extracellular deposition of amyloid fibrils. AA amyloidosis is a serious life-threatening complication of chronic rheumatic diseases responsible for increased mortality due to organ failure or infection. The main component of amyloid is the serum amyloid A precursor protein (SAA) produced by the liver as an acute phase protein. This article presents the pathogenesis of amyloidosis, which is at the core of our understanding of treatment options. Effective anti-inflammatory therapy of rheumatic diseases is the best way to prevent AA amyloidosis. Early detection of this complication leads to treatment that can effectively retard the course of the disease and may even be accompanied by regression of amyloid deposits. New hope is offered by anti-TNF-alpha antibodies or by Eprodisate, which blocks the proamyloidogenic interactions of glycosaminoglycans with SAA.
Transport of the Proinflammatory Chemokines C-C Motif Chemokine Ligand 2 (MCP-1) and C-C Motif Chemokine Ligand 5 (RANTES) across the Intact Mouse Blood-Brain Barrier Is Inhibited by Heparin and Eprodisate and Increased with Systemic Inflammation
J Pharmacol Exp Ther 2023 Jan;384(1):205-223.PMID:36310035DOI:10.1124/jpet.122.001380.
One important function of the vascular blood-brain barrier (BBB) is to facilitate neuroimmune communication. The BBB fulfills this function, in part, through its ability to transport cytokines and chemokines. C-C motif chemokine receptor 2 (CCL2) (MCP-1) and C-C motif chemokine receptor 5 (CCL5) (RANTES) are proinflammatory chemokines that mediate neuroimmune responses to acute insults and aspects of brain injury and neurodegenerative diseases; however, a blood-to-brain transport system has not been evaluated for either chemokine in vivo. Therefore, we determined whether CCL2 and CCL5 in blood can cross the intact BBB and enter the brain. Using CD-1 mice, we found that 125I-labeled CCL2 and CCL5 crossed the BBB and entered the brain parenchyma. We next aimed to identify the mechanisms of 125I-CCL2 and 125I-CCL5 transport in an in situ brain perfusion model. We found that both heparin and Eprodisate inhibited brain uptake of 125I-CCL2 and 125I-CCL5 in situ, whereas antagonists of their receptors, CCR2 or CCR5, respectively, did not, suggesting that heparan sulfates at the endothelial surface mediate BBB transport. Finally, we showed that CCL2 and CCL5 transport across the BBB increased following a single injection of 0.3 mg/kg lipopolysaccharide. These data demonstrate that CCL2 and CCL5 in the brain can derive, in part, from the circulation, especially during systemic inflammation. Further, binding to the BBB-associated heparan sulfate is a mechanism by which both chemokines can cross the intact BBB, highlighting a novel therapeutic target for treating neuroinflammation. SIGNIFICANCE STATEMENT: Our work demonstrates that C-C motif chemokine ligand 2 (CCL2) and C-C motif chemokine ligand 5 (CCL5) can cross the intact blood-brain barrier and that transport is robustly increased during inflammation. These data suggest that circulating CCL2 and CCL5 can contribute to brain levels of each chemokine. We further show that the transport of both chemokines is inhibited by heparin and Eprodisate, suggesting that CCL2/CCL5-heparan sulfate interactions could be therapeutically targeted to limit accumulation of these chemokines in the brain.