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DAPT (GSI-IX)

现货
Catalog No.
A8200
γ分泌酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 600.00
现货
10mg
¥ 700.00
现货
50mg
¥ 2,600.00
现货
500mg
¥ 9,800.00
现货

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Background

DAPT, N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl Ester, is a potent and specific inhibitor of  γ-secretase, a multimeric membrane protein complex that catalyzes proteolytic cleavage of amyloid precursor protein (APP) resulting in the accumulation of amyloi-β (Aβ) peptides which is associated with early on-set of familial Alzheimer’s disease (AD). It directly binds to the C-terminal fragment of the catalytic center of γ-secretase, presenilin (PS), especially within the transmenbrane domain 7 or more C-terminal region, resulting in the synthesis of a photoactivable DAPT derivative. Through oral administration, DAPT  dose-dependently reduced Aβ peptides levels in vivo in Plasma and cerebrospinal fluid in young (6 months old, plaque-free) and aged (17 months old, plaque-bearing) Tg2576 mice.

Reference

Thomas A. Lanz, Carol S. Himes, Giovanni Pallante, Lisa Adams, Shinji Yamazaki, Ben Amore, and Kalpana M. Merchant. The γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl Ester reduces Aβ levels in vivo in plasma and cerebrospinal fluid in young (plague-free) and aged (plaque-bearing) Tg2576 mice. The Journal of Pharmacology and Experimental Therapeutics 2003: 305 (3) 864-871

Yuichi Morohashi, Toshiyuki Kan, Yusuke Tominari, Haruhiko Fuwa, Yumiko Okamura, Naoto Watanabe, Chihiro Sato, Hideaki Natsugari, Tohru Fukuyama, Takeshi Iwatsubo, and Taisuke Tomita. C-terminal fragment of presenilin is the molecular target of a dipeptidic γ-secretase-specific inhibitor DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl Ester). The Journal of Biological Chemistry 2006: 281(21) 14670-14676

文献引用

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt432.46
Cas No.208255-80-5
FormulaC23H26F2N2O4
Synonymsgamma-Secretase Inhibitor IX, DAPT, GSI-IX
Solubility≥21.623mg/mL in DMSO, ≥16.36 mg/mL in EtOH with ultrasonic, <2.12 mg/mL in H2O
Chemical Nametert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate
SDFDownload SDF
Canonical SMILESCC(C(=O)NC(C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

SHG-44人脑胶质瘤细胞系

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

5天;1.0 μM

应用

与A组(对照组)相比,DAPT抑制了B(0.5 μM)、C(1 μM)、D(5 μM)和E(10 μM)组SHG-44细胞的增殖。B组和A组的结果具有显著差异(P<0.05)。然而,B组的细胞活力显著高于C、D和E组(P<0.05)。结果表明,逐渐增加的抑制效应与逐渐增加的DAPT浓度相关。然而,在C、D和E组之间没有差异(P>0.05)。DAPT是一种浓度依赖性的抑制剂,可明显抑制SHG-44细胞的增殖。当浓度高于1.0 μmol/L时,其对细胞的抑制作用没有明显的差异,因而1.0 μmol/L是我们优先考虑的浓度。

动物实验[2]:

动物模型

雄性Balb/C小鼠

剂量

10 mg/kg/day;皮下注射

应用

CT26结肠腺癌细胞(5×105)悬浮在500 μL的磷酸盐缓冲液(PBS)中,皮下接种到所有小鼠的背部。DAPT显著减少血清sVEGFR1,然而无法改变对照小鼠血清中VEGF的浓度。肿瘤的免疫组化研究表明,DAPT减少CD31阳性细胞的数量(280.6 ± 81 vs. 386 ± 59.9 CD31阳性细胞/mm2),尽管在统计学上是不显著的。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Liu X, Xu Q R, Xie W F, et al. DAPT suppresses the proliferation of human glioma cell line SHG-44[J]. Asian Pacific journal of tropical medicine, 2014, 7(7): 552-556.

[2] Kalantari E, Saeidi H, Kia N S, et al. Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice[J]. Advanced biomedical research, 2013, 2.

生物活性

描述 DAPT (GSI-IX)是一种新型的γ分泌酶抑制剂,在HEK 293细胞中的IC50值为20 nM。
靶点          
IC50 20 nM          

质量控制

化学结构

DAPT

相关生物数据

DAPT
The result shows the level of Aβ40 and Aβ42 decreased as the DAPT concentration increased. Compared with Aβ42, the level of Aβ420 decreased more rapidly with increasing DAPT concentration.

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DAPT
The Neuro-2A cells (transfected with Klotho) were treated with DAPT for 16 h. The transfected Neuro-2A without DAPT treatment was assigned as control. Un-transfected Neruo-2A was assigned as wild type cells (wt). The protein levels of Klotho and Klotho (sub) from cells lysate were analyzed using Klotho and Flag antibody respectively. Gamma-secretase inhibitor DAPT could cleave Klotho stub. After treatment with DAPT, 5 kDa fragment was found in transfected cells, which was not seen in wt and control group.

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DAPT

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DAPT

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DAPT

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