DAPT (GSI-IX)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
DAPT，N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl Ester，是一种有效的、特异性的γ分泌酶抑制剂。γ分泌酶是一个多聚膜蛋白复合体，催化淀粉样前体蛋白（APP）的水解，从而导致β淀粉样蛋白（Aβ）的积累，其与家族性阿尔兹海默病（AD）的早期症状相关联。DAPT直接结合γ分泌酶催化中心的C端片段，即presenilin (PS)，尤其是第7个跨膜结构域或更大的C-末端区域，从而合成一个光活化的DAPT衍生物。
在幼年（6个月大，无斑块）和老年（17个月大，有斑块）Tg2576小鼠中，DAPT口服给药可以剂量依赖性的减少血浆和脑脊液中Aβ肽的水平。
参考文献：
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-phenylg
-lycine t-butyl Ester). The Journal of Biological Chemistry 2006: 281(21) 14670-14676
- 1. Julia Sidor, Megan Gillette, et al. "Role of Presenilin-1 in Aggressive Human Melanoma." Int J Mol Sci. 2022 Apr 28;23(9):4904. PMID: 35563300
- 2. Xiaoya An, Guoliang Wang, et al. "Novel cell culture paradigm prolongs mouse corneal epithelial cell proliferative activity in vitro and in vivo." Front Cell Dev Biol. 2021 Jun 30;9:675998. PMID: 34277619
- 3. Shanfeng Sun, Songsong Jiang, et al. "Cholera toxin induces food allergy through Th2 cell differentiation which is unaffected by Jagged2." Life Sci. 2020 Oct 1;263:118514. PMID: 33010283
- 4. Weigang He, Jinxia Sun, et al. "Andrographolide exerts anti‐inflammatory effects in Mycobacterium tuberculosis‐infected macrophages by regulating the Notch1/Akt/NF‐κB axis." J Leukoc Biol. 2020 Dec;108(6):1747-1764. PMID: 32991757
- 5. Shu min Lv, Hongwen Cai, et al. "Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway." Int J Mol Med. 2020 Oct;46(4):1347-1358. PMID: 32945357
- 6. Ireland AS, Micinski AM, et al. "MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate." Cancer Cell. 2020 Jul 13;38(1):60-78.e12. PMID: 32473656
- 7. Zhu M, Li Y, et al. "Effects of bisphenol A and its alternative bisphenol F on Notch signaling and intestinal development: A novel signaling by which bisphenols disrupt vertebrate development." Environ Pollut. 2020;263(Pt B):114443. PMID: 32311622
- 8. Zhu M, Niu Y, et al. "Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models." Chem Res Toxicol. 2020;10.1021/acs.chemrestox.9b00528. PMID: 32041402
- 9. Jennifer E. Speer, Yuli Wang, et al. "Evaluation of human primary intestinal monolayers for drug metabolizing capabilities." Journal of Biological Engineering volume 13, Article number: 82 (2019)
- 10. Wu J, Wang X, et al. "Allyl isothiocyanate may reverse the expression of MRP1 in COPD rats via the Notch1 signaling pathway." Arch Pharm Res. 2019 Sep 30. PMID: 31571144
- 11. Speer JE, Gunasekara DB, et al. "Molecular transport through primary human small intestinal monolayers by culture on a collagen scaffold with a gradient of chemical cross-linking." J Biol Eng. 2019 Apr 27;13:36. PMID: 31061676
- 12. Azimi M, Brown NL. "Jagged1 protein processing in the developing mammalian lens." Biol Open. 2019 Mar 26;8(3). pii: bio041095. PMID: 30890522
- 13. Wu F, Wu D, et al. "Generation of hepato-biliary organoids from human induced pluripotent stem cells." J Hepatol. 2019 Jan 7. pii: S0168-8278(19)30002-9. PMID: 30630011
- 14. MXinwei Feng, Junfeng Lu, et al. "Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells." Front. Cell. Infect. Microbiol., 19 June 2018.
- 15. Tang J, Zhou H, et al. "Dual-Mode Imaging-Guided Synergistic Chemo- and Magnetohyperthermia Therapy in a Versatile Nanoplatform To Eliminate Cancer Stem Cells." ACS Appl Mater Interfaces.2017 Jul 19;9(28):23497-23507. PMID: 28661121
- 16. Fan Y, Gao X, Chen J, et al. "HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway." J Neurosci. 2016 Nov 2;36(44):11362-11373. PMID: 27807176
- 17. Zhou, Xuanxuan, et al. "Tetrahydroxystilbene glucoside extends mouse lifespan via up-regulating neural Klotho and down-regulating neural insulin/insulin-like growth factor 1." Neurobiology of Aging (2014).
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 432.46 |
| Cas No. | 208255-80-5 |
| Formula | C23H26F2N2O4 |
| Synonyms | gamma-Secretase Inhibitor IX, DAPT, GSI-IX |
| Solubility | ≥21.62 mg/mL in DMSO; insoluble in H2O; ≥16.36 mg/mL in EtOH with ultrasonic |
| Chemical Name | tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate |
| SDF | Download SDF |
| Canonical SMILES | CC(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 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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（P0.05）。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. |
|
| 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 | Aβ | |||||
| IC50 | 20 nM | |||||
质量控制和MSDS
- 批次:
化学结构
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
