NEP
(Synonyms: 倍氯米松,VDP-green (NEP)) 目录号 : GC61589
NEP(VDP-green(NEP))是一种基于分子内电荷转移(ICT)机制的感应荧光探针，用于感应含邻二硫醇的蛋白质(VDPs)。NEP在活细胞和动物体内对VDPs表现出高选择性，并显示强绿色荧光信号(Λex/Λem=430/535nm)。NEP具有用于帕金森氏症研究的潜力。
Cas No.:2414276-32-5
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
NEP (VDP-green (NEP)) is a turn-on fluorescent probe based on the intramolecular charge transfer (ICT) mechanism for sensing vicinal dithiol-containing proteins (VDPs). NEP is exhibits high selectivity toward VDPs in live cells and in vivo and displays a strong green fluorescence signal (Λex/Λem=430/535 nm). NEP has the potential for parkinsonism[1].
NEP (1-30 μM; 6 hours) has no or little cytotoxicity in HepG2 and PC12 cells[1]. NEP (10 μM; 4 hours) causes the fluorescence intensity to decrease gradually in PC12 cells pretreated with 6-OHDA (0, 50, 100, and 200 μM; for 30 min)[1]. NEP contains a dithiarsolane moiety (five-membered As-S ring) as the receptor of VDPs. In the presence of VDPs, NEP displays a strong green fluorescence signal produced by the cyclic dithiarsolane cleavage and subsequent intramolecular cyclization to liberate the fluorophore. NEP maintains a reliable fluorescence response within the range of pH 7-10[1].
NEP (10 μM; for 4 h) causes the obvious green signal in zebrafishes (4 day old)[1].
[1]. Guodong Hu, et al. Decrease of Protein Vicinal Dithiols in Parkinsonism Disclosed by a Monoarsenical Fluorescent Probe. Anal Chem. 2020 Mar 17;92(6):4371-4378.
| Cas No. | 2414276-32-5 | SDF | |
| 别名 | 倍氯米松,VDP-green (NEP) | ||
| Canonical SMILES | O=C(N1CCCC)C2=C3C(C(NC(OCC4S[As](SC4)C5=CC=C(C=C5)NC(CCN)=O)=O)=CC=C3C1=O)=CC=C2 | ||
| 分子式 | C29H31AsN4O5S2 | 分子量 | 654.63 |
| 溶解度 | 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 | 1.5276 mL | 7.6379 mL | 15.2758 mL |
| 5 mM | 0.3055 mL | 1.5276 mL | 3.0552 mL |
| 10 mM | 0.1528 mL | 0.7638 mL | 1.5276 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。
The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function
Bioessays 2001 Mar;23(3):261-9.PMID:11223883DOI:10.1002/1521-1878(200103)23:3<261::AID-BIES1036>3.0.CO;2-K.
Neprilysin (NEP), a thermolysin-like zinc metalloendopeptidase, plays an important role in turning off peptide signalling events at the cell surface. It is involved in the metabolism of a number of regulatory peptides of the mammalian nervous, cardiovascular, inflammatory and immune systems. Examples include enkephalins, tachykinins, natriuretic and chemotactic peptides. NEP is an integral plasma membrane ectopeptidase of the M13 family of zinc peptidases. Other related mammalian NEP-like enzymes include the endothelin-converting enzymes (ECE-1 and ECE-2), KELL and PEX. A number of novel mammalian homologues of NEP have also recently been described. NEP family members are potential therapeutic targets, for example in cardiovascular and inflammatory disorders, and potent and selective inhibitors such as phosphoramidon have contributed to understanding enzyme function. Inhibitor design should be facilitated by the recent three-dimensional structural solution of the NEP-phosphoramidon complex. For several of the family members, however, a well-defined physiological function or substrate is lacking. Knowledge of the complete genomes of Caenorhabditis elegans and Drosophila melanogaster allows the full complement of NEP-like activities to be analysed in a single organism. These model organisms also provide convenient systems for examining cell-specific expression, developmental and functional roles of this peptidase family, and reveal the power of functional genomics.
Emerging roles for the influenza A virus nuclear export protein (NEP)
PLoS Pathog 2012;8(12):e1003019.PMID:23236273DOI:10.1371/journal.ppat.1003019.
Influenza virus is a major human and animal pathogen causing seasonal epidemics and occasional pandemics in the human population that are associated with significant morbidity and mortality. Influenza A virus, a member of the orthomyxovirus family, contains an RNA genome with a coding capacity for a limited number of proteins. In addition to ensuring the structural integrity of virions, these viral proteins facilitate the replication of virus in the host cell. Consequently, viral proteins often evolve to perform multiple functions, the influenza A virus nuclear export protein (NEP) (also referred to as non-structural protein 2, or NS2) being an emerging example. NEP was originally implicated in mediating the nuclear export of viral ribonucleoprotein (RNP) complexes, which are synthesized in the infected cell nucleus and are assembled into progeny virions at the cell membrane. However, since then, new and unexpected roles for NEP during the influenza virus life cycle have started to emerge. These recent studies have shown NEP to be involved in regulating the accumulation of viral genomic vRNA and antigenomic cRNA as well as viral mRNA synthesized by the viral RNA-dependent RNA polymerase. Subsequently, this regulation of viral RNA transcription and replication by NEP was shown to be an important factor in the adaptation of highly pathogenic avian H5N1 influenza viruses to the mammalian host. Unexpectedly, NEP has also been implicated in recruiting a cellular ATPase to the cell membrane to aid the efficient release of budding virions. Accordingly, NEP is proposed to play multiple biologically important roles during the influenza virus life cycle.
Neprilysin expression and functions in development, ageing and disease
Mech Ageing Dev 2020 Dec;192:111363.PMID:32987038DOI:10.1016/j.mad.2020.111363.
Neprilysin (NEP) is an integral membrane-bound metallopeptidase with a wide spectrum of substrates and physiological functions. It plays an important role in proteolytic processes in the kidney, cardiovascular regulation, immune response, cell proliferation, foetal development etc. It is an important neuropeptidase and amyloid-degrading enzyme which makes NEP a therapeutic target in Alzheimer's disease (AD). Moreover, it plays a preventive role in development of cancer, obesity and type-2 diabetes. Recently a role of NEP in COVID-19 pathogenesis has also been suggested. Despite intensive research into NEP structure and functions in different organisms, changes in its expression and regulation during brain development and ageing, especially in age-related pathologies, is still not fully understood. This prevents development of pharmacological treatments from various diseases in which NEP is implicated although recently a dual-acting drug sacubitril-valsartan (LCZ696) combining a NEP inhibitor and angiotensin receptor blocker has been approved for treatment of heart failure. Also, various natural compounds capable of upregulating NEP expression, including green tea (EGCG), have been proposed as a preventive medicine in prostate cancer and AD. This review summarizes the existing literature and our own research on the expression and activity of NEP in normal brain development, ageing and under pathological conditions.
Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease
Front Aging Neurosci 2013 Dec 23;5:98.PMID:24391587DOI:10.3389/fnagi.2013.00098.
One of the characteristic hallmarks of Alzheimer's disease (AD) is an accumulation of amyloid β (Aβ) leading to plaque formation and toxic oligomeric Aβ complexes. Besides the de novo synthesis of Aβ caused by amyloidogenic processing of the amyloid precursor protein (APP), Aβ levels are also highly dependent on Aβ degradation. Several enzymes are described to cleave Aβ. In this review we focus on one of the most prominent Aβ degrading enzymes, the zinc-metalloprotease Neprilysin (NEP). In the first part of the review we discuss beside the general role of NEP in Aβ degradation the alterations of the enzyme observed during normal aging and the progression of AD. In vivo and cell culture experiments reveal that a decreased NEP level results in an increased Aβ level and vice versa. In a pathological situation like AD, it has been reported that NEP levels and activity are decreased and it has been suggested that certain polymorphisms in the NEP gene result in an increased risk for AD. Conversely, increasing NEP activity in AD mouse models revealed an improvement in some behavioral tests. Therefore it has been suggested that increasing NEP might be an interesting potential target to treat or to be protective for AD making it indispensable to understand the regulation of NEP. Interestingly, it is discussed that the APP intracellular domain (AICD), one of the cleavage products of APP processing, which has high similarities to Notch receptor processing, might be involved in the transcriptional regulation of NEP. However, the mechanisms of NEP regulation by AICD, which might be helpful to develop new therapeutic strategies, are up to now controversially discussed and summarized in the second part of this review. In addition, we review the impact of AICD not only in the transcriptional regulation of NEP but also of further genes.
Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?
J Neurochem 2002 Apr;81(1):1-8.PMID:12067222DOI:10.1046/j.1471-4159.2002.00855.x.
The steady-state level of amyloid beta-peptide (Abeta) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the beta- and gamma-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting A,beta degradation may provide a novel approach to the therapy of Alzheimer's disease.