Home>>Signaling Pathways>> Neuroscience>> Amyloid β>>gamma-Secretase Modulators

gamma-Secretase Modulators Sale

(Synonyms: (E)-(4R,9AS)-7-[3-甲氧基-4-(4-甲基-1H-咪唑-1-基)苯亚甲基]-4-(3,4,5-三氟苯基六氢吡啶并[2,1-C][1,4]嗪-6-酮,Amyloid-β production inhibitor; γ-Secretase Modulators) 目录号 : GC36110

gamma-Secretase Modulators (Amyloid-β production inhibitor)是淀粉状蛋白β生成抑制剂,可作用于阿尔茨海默病。

gamma-Secretase Modulators Chemical Structure

Cas No.:937812-80-1

规格 价格 库存 购买数量
5mg
¥4,210.00
现货
10mg
¥8,169.00
现货
50mg 待询 待询
100mg 待询 待询

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

gamma-Secretase Modulators (Amyloid-β production inhibitor) is a Amyloid-β production inhibitor. gamma-Secretase Modulators is useful for Alzheimer's disease.IC50 value:Target: γ-secretase modulator

[1]. Watahiki H, Yagishita S, Futai E, Ishiura S.CTF1-51, a truncated carboxyl-terminal fragment of amyloid precursor protein, suppresses the effects of Aβ42-lowering γ-secretase modulators.Neurosci Lett. 2012 Sep 27;526(2):96-9. Epub 2012 Aug 23. [2]. Wanngren J, Ottervald J, Parpal S, Portelius E, Str•mberg K, Borgeg•rd T, Klintenberg R, JurÉus A, Blomqvist J, Blennow K, Zetterberg H, Lundkvist J, Rosqvist S, Karlstr•m H.Second generation γ-secretase modulators exhibit different modulation of Notch β [3]. Wagner SL, Tanzi RE, Mobley WC, Galasko D.Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease.Arch Neurol. 2012 Jul 16:1-4. [4]. Bulic B, Ness J, Hahn S, Rennhack A, Jumpertz T, Weggen S.Chemical Biology, Molecular Mechanism and Clinical Perspective of γ-Secretase Modulators in Alzheimer's Disease.Curr Neuropharmacol. 2011 Dec;9(4):598-622. [5]. Kretner, Benedikt; Fukumori, Akio; Gutsmiedl, Amelie; Page, Richard M.; Luebbers, Thomas; Galley, Guido; Baumann, Karlheinz; Haass, Christian; Steiner, Harald. Attenuated A.beta.42 Responses to Low Potency .gamma.-Secretase Modulators Can Be Overcome for

Chemical Properties

Cas No. 937812-80-1 SDF
别名 (E)-(4R,9AS)-7-[3-甲氧基-4-(4-甲基-1H-咪唑-1-基)苯亚甲基]-4-(3,4,5-三氟苯基六氢吡啶并[2,1-C][1,4]嗪-6-酮,Amyloid-β production inhibitor; γ-Secretase Modulators
Canonical SMILES O=C1N2[C@@H](COC[C@]2([H])CC/C1=C\C3=CC(OC)=C(C=C3)N4C=NC(C)=C4)C5=CC(F)=C(F)C(F)=C5
分子式 C26H24F3N3O3 分子量 483.48
溶解度 DMSO: ≥ 100 mg/mL (206.83 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。
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。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.0683 mL 10.3417 mL 20.6834 mL
5 mM 0.4137 mL 2.0683 mL 4.1367 mL
10 mM 0.2068 mL 1.0342 mL 2.0683 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

Research Update

gamma-Secretase Modulators

Curr Alzheimer Res 2007 Dec;4(5):571-3.PMID:18220525DOI:10.2174/156720507783018299.

gamma-Secretase is responsible for the final cut of the amyloid beta-peptide (Abeta) precursor (APP) to produce the Abeta peptide implicated the pathogenesis of Alzheimer's disease (AD). Thus, this protease is a top target for the development of AD therapeutics. gamma-Secretase is a complex of four different integral membrane proteins, with the multi-pass presenilin being the catalytic component of a novel intramembrane-cleaving aspartyl protease. gamma-Secretase cleaves other substrates besides APP, the most notorious being the Notch receptor that is required for many cell differentiation events. Because proteolysis of Notch by gamma-secretase is essential for Notch signaling, interference with this process by gamma-secretase inhibitors can cause severe toxicities. Thus, the potential of gamma-secretase as therapeutic target likely depends on the ability to selectively inhibit Abeta production without hindering Notch proteolysis. The discovery of compounds capable of such allosteric modulation of the protease activity has revived gamma-secretase as an attractive target. Structural modification of these gamma-Secretase Modulators through medicinal chemistry should lead to in vivo active agents suitable for clinical trials.

γ-Secretase modulators show selectivity for γ-secretase-mediated amyloid precursor protein intramembrane processing

J Cell Mol Med 2022 Feb;26(3):880-892.PMID:34931449DOI:10.1111/jcmm.17146.

The aggregation of β-amyloid peptide 42 results in the formation of toxic oligomers and plaques, which plays a pivotal role in Alzheimer's disease pathogenesis. Aβ42 is one of several Aβ peptides, all of Aβ30 to Aβ43 that are produced as a result of γ-secretase-mediated regulated intramembrane proteolysis of the amyloid precursor protein. γ-Secretase modulators (GSMs) represent a promising class of Aβ42-lowering anti-amyloidogenic compounds for the treatment of AD. gamma-Secretase Modulators change the relative proportion of secreted Aβ peptides, while sparing the γ-secretase-mediated processing event resulting in the release of the cytoplasmic APP intracellular domain. In this study, we have characterized how GSMs affect the γ-secretase cleavage of three γ-secretase substrates, E-cadherin, ephrin type A receptor 4 (EphA4) and ephrin type B receptor 2 (EphB2), which all are implicated in important contexts of cell signalling. By using a reporter gene assay, we demonstrate that the γ-secretase-dependent generation of EphA4 and EphB2 intracellular domains is unaffected by GSMs. We also show that γ-secretase processing of EphA4 and EphB2 results in the release of several Aβ-like peptides, but that only the production of Aβ-like proteins from EphA4 is modulated by GSMs, but with an order of magnitude lower potency as compared to Aβ modulation. Collectively, these results suggest that GSMs are selective for γ-secretase-mediated Aβ production.

Piperidine-derived gamma-Secretase Modulators

Bioorg Med Chem Lett 2010 Feb 1;20(3):1306-11.PMID:20056541DOI:10.1016/j.bmcl.2009.08.072.

This Letter details the SAR of a novel series of piperidine-derived gamma-Secretase Modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Abeta42, increase Abeta38 and have no effect on Abeta40 levels. Furthermore, 10h demonstrated excellent pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS penetration in the mouse.

Substrate-targeting gamma-Secretase Modulators

Nature 2008 Jun 12;453(7197):925-9.PMID:18548070DOI:10.1038/nature07055.

Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-Secretase Modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinylated photoactivatable GSMs. GSM photoprobes did not label the core proteins of the gamma-secretase complex, but instead labelled the beta-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-beta peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP gamma-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28-36 of amyloid-beta, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-beta act as GSMs, and some GSMs alter the production of cell-derived amyloid-beta oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Abeta42 production and inhibition of amyloid-beta aggregation, which may synergistically reduce amyloid-beta deposition in Alzheimer's disease. These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets.