Emedastine-13C-d3 (fumarate)
目录号 : GC49063
An internal standard for the quantification of emedastine
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Emedastine-13C-d3 is intended for use as an internal standard for the quantification of emedastine by GC- or LC-MS. Emedastine is a histamine H1 receptor antagonist (Ki = 1.3 nM).1 It is selective for histamine H1 over H2 and H3 receptors (Kis = 49 and 12.43 µM, respectively), as well as α1-, α2-, and β1-adrenergic and dopamine D1 and D2 receptors, and the serotonin (5-HT) receptor subtypes 5-HT1 and 5-HT2 at 10 µM.1,2 Emedastine inhibits histamine-induced phosphoinositide turnover and intracellular calcium mobilization in primary human conjunctival epithelial cells (HCECs; IC50s = 1.6 and 2.9 nM, respectively).3 It also inhibits histamine-stimulated secretion of IL-6, IL-8, and GM-CSF by primary HCECs (IC50s = 2.23, 3.42, and 1.50 nM, respectively).4 Ocular application of emedastine prior to histamine challenge inhibits vascular permeability in guinea pigs.2 Formulations containing emedastine have been used in the treatment of allergic conjunctivitis.
1.Sharif, N.A., Su, S.X., and Yanni, J.M.Emedastine: A potent, high affinity histamine H1-receptor-selective antagonist for ocular use: Receptor binding and second messenger studiesJ. Ocul. Pharmacol.10(4)653-664(1994) 2.Yanni, J.M., Stephens, D.J., Parnell, D.W., et al.Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist for topical ocular useJ. Ocul. Pharmacol.10(4)665-675(1994) 3.Sharif, N.A., Xu, S.X., Magnino, P.E., et al.Human conjunctival epithelial cells express histamine-1 receptors coupled to phosphoinositide turnover and intracellular calcium mobilization: Role in ocular allergic and inflammatory diseasesExp. Eye Res.63(2)169-178(1996) 4.Weimer, L.K., Gamache, D.A., and Yanni, J.M.Histamine-stimulated cytokine secretion from human conjunctival epithelial cells: Inhibition by the histamine H1 antagonist emedastineInt. Arch. Allergy. Immunol.115(4)288-293(1998)
| Cas No. | N/A | SDF | |
| Canonical SMILES | CCOCCN1C2=CC=CC=C2N=C1N3CCCN([13C]([2H])([2H])[2H])CC3.OC(/C=C/C(O)=O)=O | ||
| 分子式 | C16[13C]H23D3N4O·C4H4O4 | 分子量 | 422.5 |
| 溶解度 | Acetonitrile: soluble,DMSO: soluble,Methanol: soluble | 储存条件 | -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 | 2.3669 mL | 11.8343 mL | 23.6686 mL |
| 5 mM | 0.4734 mL | 2.3669 mL | 4.7337 mL |
| 10 mM | 0.2367 mL | 1.1834 mL | 2.3669 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。
Dimethyl fumarate: A review of preclinical efficacy in models of neurodegenerative diseases
Eur J Pharmacol 2022 Jul 5;926:175025.PMID:35569547DOI:10.1016/j.ejphar.2022.175025.
Dimethyl fumarate (DMF) is an antioxidative and anti-inflammatory drug approved for treatment of multiple sclerosis and psoriasis; however, beneficial effects of DMF have also been found in other inflammatory diseases and cancers. DMF is a prodrug that is immediately hydrolysed to monomethyl fumarate (MMF) in vivo. Both fumarates activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, and Nrf2 is a key transcription factor of the antioxidant response. The immunosuppressive and anti-inflammatory actions of DMF occur through several mechanisms: via inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and by downregulation of aerobic glycolysis and pyroptosis in activated myeloid and lymphoid cells. MMF is also an agonist of hydroxycarboxylic acid receptor 2 (HCAR2). Differences in the strength of effects and mechanisms of action of both fumarates are discussed. The aim of this review was to analyse and compare the neuroprotective, antioxidative and anti-inflammatory effects of DMF and its active metabolite, MMF, in cellular (in vitro) and animal models of neurodegenerative diseases (NDs), other than multiple sclerosis. There are more than twenty studies that currently represent this field. Most of the studies are concerned with cellular or animal models of Alzheimer's disease (AD) and Parkinson's disease (PD), one utilized a mouse model of Huntington's disease (HD) and one clinical trial was carried out with amyotrophic lateral sclerosis (ALS) patients. The discrepancies in the results of the various studies are discussed, and issues requiring further research have been identified.
Diroximel fumarate to treat multiple sclerosis
Drugs Today (Barc) 2020 Jul;56(7):431-437.PMID:32648853DOI:10.1358/dot.2020.56.7.3151521.
On October 29, 2019, the Food and Drug Administration (FDA) of the United States approved diroximel fumarate (DRF) as an oral fumarate for the treatment of relapsing forms of multiple sclerosis. Another oral fumarate, dimethyl fumarate (DMF), was approved for the same indication on March 27, 2013. Prior to its approval, DRF did not undergo rigorous testing to determine its efficacy, as its active metabolite, monomethyl fumarate, is the same as that of DMF (bioequivalency). The efficacy, safety and tolerability of DMF have previously been demonstrated in a number of clinical trials and real-world studies. For DRF, one phase III study has been completed, and another is in progress to determine its safety, tolerability and efficacy. In this paper, we review the pharmacology, pharmacokinetics, metabolism, clinical studies and drug safety of DRF.
Photoinducible Oncometabolite Detection
Chembiochem 2019 Feb 1;20(3):360-365.PMID:30358041DOI:10.1002/cbic.201800651.
Dysregulated metabolism can fuel cancer by altering the production of bioenergetic building blocks and directly stimulating oncogenic gene-expression programs. However, relatively few optical methods for the direct study of metabolites in cells exist. To address this need and facilitate new approaches to cancer treatment and diagnosis, herein we report an optimized chemical approach to detect the oncometabolite fumarate. Our strategy employs diaryl tetrazoles as cell-permeable photoinducible precursors to nitrileimines. Uncaging these species in cells and cell extracts enables them to undergo 1,3-dipolar cycloadditions with endogenous dipolarophile metabolites such as fumarate to form pyrazoline cycloadducts that can be readily detected by their intrinsic fluorescence. The ability to photolytically uncage diaryl tetrazoles provides greatly improved sensitivity relative to previous methods, and enables the facile detection of dysregulated fumarate metabolism through biochemical activity assays, intracellular imaging, and flow cytometry. Our studies showcase an intersection of bioorthogonal chemistry and metabolite reactivity that can be applied for biological profiling, imaging, and diagnostics.
BG-12 in multiple sclerosis
Semin Neurol 2013 Feb;33(1):56-65.PMID:23709213DOI:10.1055/s-0033-1343796.
Dimethyl fumarate (DMF) is an orally administered agent that has been used for over 40 years for the treatment of psoriasis. Recent work demonstrates both DMF immunomodulatory and neuroprotective actions in vitro and in animal models of autoreactive central nervous system inflammation and neurodegeneration. DMF acts through chemical modification of the repressor protein Keap1, allowing stabilization and nuclear translocation of the transcription factor Nrf2, with subsequent downstream activation of a cascade of several cytoprotective and antioxidant pathways. Additionally, suppression of transcription factor NF-κB-mediated proinflammatory signaling results in the inhibition of proinflammatory responses and induction of anti-inflammatory cytokines. BG-12 is an orally administered, enteric-coated microtablet preparation of DMF. In two phase III, relapsing-remitting multiple sclerosis (MS) trials, BG-12 led to a 44 to 53% reduction in annualized relapse rate and a 71 to 85% reduction in new T2 lesions on magnetic resonance imaging. The most common side effects of BG-12 are cutaneous flushing and gastrointestinal symptoms, with the highest incidence in the first month after starting treatment. No serious safety signals were seen during the phase II and III trials, including no increased risk of opportunistic infections or cancer. Altogether, BG-12's novel mechanism of action appears to provide a favorable balance of efficacy, safety, and tolerability for treatment of relapsing MS.
Dimethyl fumarate for treating relapsing multiple sclerosis
Expert Opin Drug Saf 2015 Jan;14(1):161-70.PMID:25382392DOI:10.1517/14740338.2015.977251.
Introduction: Outcomes of two large double-blind placebo-controlled studies of oral dimethyl fumarate (DMF) in multiple sclerosis (MS) provided the basis for its marketing approval as Tecfidera® by the US FDA in early 2013 and the European Medicines Agency in February 2014. The safety of DMF is complemented by experience in the use of an oral mixture of fumaric acid esters, including DMF for psoriasis (Fumaderm®; DMF and monoethyl fumarate [DMF-MEF]) licensed in Germany in 1994. Areas covered: This article reviews the pivotal trials leading to the approval of DMF for MS and the pharmacological literature related to the extensive use of oral fumaric acid esters for psoriasis over the last quarter century. Anecdotal reports of serious adverse reactions to DMF-MEF are also reviewed in this report. Expert opinion: DMF is generally safe and well tolerated. Flushing and gastrointestinal side effects are relatively common for the approved DMF dose but are ordinarily mild and self-limited. No increase in malignancies has been reported despite theoretical concerns. Although progressive multifocal encephalopathy has been reported anecdotally in 5 of > 196,000 patient-years of experience with fumaric acid esters, none of the 65,000 DMF MS patients treated in the first year has been affected. Appendix to the abstract: Subsequent to the acceptance of this article for publication, the manufacturer has notified physicians of the death of one patient from PML complicating use of DMF in the DEFINE study extension (ENDORSE). This does not alter the expert opinion rendered regarding the safety of DMF. We await the outcomes and recommendations from the ongoing investigation into this case.