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DAPT,γ-分泌酶抑制剂

γ-分泌酶抑制剂
规格或纯度: ≥98%
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基本描述

规格或纯度 ≥98%
英文名称 DAPT
别名 N-[N-(3,5-二氟苯乙酰)-L-丙氨酰]-S-苯甘氨酸叔丁酯；(3,5-二氟苯乙酰基)-Ala-Phg-OtBu；(3,5-二氟苯乙酰基)-L-丙氨酰基-L-2-苯基甘氨酸叔丁酯
英文别名 GSI-IX;GSI IX;γ-Secretase Inhibitor IX; LY-374973; N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester;(3,5-Difluorophenylacetyl)-L-alanyl-L-2-phenylglycine tert-Butyl Ester;(3,5-Difluorophenylacetyl)-Ala-Phg-OtBu
生化机理 DAPT is a potent and specific inhibitor of γ-secretase. It has been shown to cause a reduction in Aβ40 and Aβ42 levels in human primary neuronal cultures (IC50 values are 115 and 200 nM for total Aβ40 and Aβ42 respectively). There is evidence that DAPT does not effect APPα and APPβ levels. It mimics notch signaling deficiencies at morphological, molecular and biochemical levels and has been shown to block notch signaling in hybrid human-mouse foetal thymus organ culture (FTOC).γ-Secretase inhibitor. Inhibits Notch signalling in vitro . Inhibits total Aβ and Aβ42 production in human primary cultures (IC 50 values are 115 and 200 nM, respectively) with no effect on APPα and APPβ levels. Blood-brain barrier permeable.
储存温度 2-8°C储存,充氩
运输条件 冰袋运输
备注 5mg卖完停产，不再备货；如果有可能，您尽量在使用的当天配置溶液，并在当天使用完它。但是，如果您需要预先配制储备溶液，我们建议您将溶液等份保存在-20°C的密封小瓶中。通常，它们最多可以使用一个月。在使用前和打开样品瓶之前，我们建议您让您的产品在室温下平衡至少1小时。需要更多关于溶解度，用法和处理的建议吗？请访问我们的常见问题（FAQ）页面以获取更多详细信息。
产品介绍

DAPT (GSI-IX)是一种新型γ-分泌酶抑制剂，抑制HEK 293细胞中全部Aβ产量， IC50为20 nM。A potent and specific inhibitor of γ-secretase.

DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells.
A potent and specific inhibitor of γ-secretase.

名称和标识符

IUPAC Name tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate
INCHI InChI=1S/C23H26F2N2O4/c1-14(26-19(28)12-15-10-17(24)13-18(25)11-15)21(29)27-20(16-8-6-5-7-9-16)22(30)31-23(2,3)4/h5-11,13-14,20H,12H2,1-4H3,(H,26,28)(H,27,29)/t14-,20-/m0/s1
InChi Key DWJXYEABWRJFSP-XOBRGWDASA-N
Canonical SMILES CC(C(=O)NC(C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F
分子式

C23H26F2N2O4
关联CAS 208255-80-5
PubChem CID 5311272
分子量 432.46

化学和物理性质

溶解性 Soluble in DMSO (15 mg/mL), ethanol (~1 mg/mL), dichloromethane, DMF (~25 mg/mL), and 1:9 solution of DMF:PBS(pH 7.2) (~0.1 mg/mL).
敏感性 对热敏感

安全信息

WGK Germany 3
个人防护装备 Eyeshields， Gloves， type N95 (US)， type P1 (EN143) respirator filter

关联配体

Ligand ID 11363
名称 DAPT
别名 gamma-Secretase Inhibitor IX
类别 Synthetic organic
学名 tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate
生物活性评价 DAPT displaces the selective γ-secretase inhibitor IN973 from the enzyme complex in human THP-1 cells in vitro (IC50 6.3 nM) . It reduces the levels of β-amyloid in a mouse model of Alzheimer's disease ,
评价 DAPT is a γ-secretase inhibitor that is used experimentally to inhibit NOTCH pathway signalling. Chemically it is a modified di-peptide (IUPAC Condensed name Unk-Ala-Phg-OtBu).

参考文献

1. Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ et al..  (2001)  Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain..  J Neurochem,  76  (1):  (173-81).  [PMID:11145990]
2. Iben LG, Olson RE, Balanda LA, Jayachandra S, Robertson BJ, Hay V, Corradi J, Prasad CV, Zaczek R, Albright CF et al..  (2007)  Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology..  J Biol Chem,  282  (51):  (36829-36).  [PMID:17932033]
3. Czerwinski A, Valenzuela F, Afonine P, Dauter M, Dauter Z.  (2010)  N-{N-[2-(3,5-Difluorophenyl)acetyl]-(S)-alanyl}-(S)-phenylglycine tert-butyl ester (DAPT): an inhibitor of γ-secretase, revealing fine electronic and hydrogen-bonding features..  Acta Crystallogr C,  66  (Pt 12):  (o585-8).  [PMID:21123889]
4. Fukusumi H et al..  (2021)  Alpha-synuclein dynamics in induced pluripotent stem cell-derived dopaminergic neurons from a Parkinson's disease patient (PARK4) with SNCA triplication..  FEBS Open Bio,  11  (2):  (354-366).  [PMID:33301617]
5. Vladar EK et al..  (2016)  Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation..  JCI Insight,  1  (13):  ().  [PMID:27570836]
6. Wang P et al..  (2017)  Basic fibroblast growth factor reduces scar by inhibiting the differentiation of epidermal stem cells to myofibroblasts via the Notch1/Jagged1 pathway..  Stem Cell Res Ther,  8  ():  (114).  [PMID:28511663]
7. Loo LSW et al..  (2020)  BCL-xL/BCL2L1 is a critical anti-apoptotic protein that promotes the survival of differentiating pancreatic cells from human pluripotent stem cells..  Cell Death Dis,  11  (5):  (378).  [PMID:32424151]
8. Chen X et al..  (2019)  C1q/tumor necrosis factor-related protein-3 improves renal fibrosis via inhibiting notch signaling pathways..  J Cell Physiol,  234  (12):  (22352-22364).  [PMID:31074042]
9. McKinley KL et al..  (2018)  Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia..  Elife,  7  ():  ().  [PMID:29897330]
10. Zhan C et al..  (2021)  Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development..  Exp Ther Med,  22  (3):  (972).  [PMID:34335914]
11. Zhou L et al..  (2020)  Emodin inhibiting neutrophil elastase-induced epithelial-mesenchymal transition through Notch1 signalling in alveolar epithelial cells..  J Cell Mol Med,  24  (20):  (11998-12007).  [PMID:32935466]
12. Gahan JM et al..  (2017)  Functional studies on the role of Notch signaling in Hydractinia development..  Dev Biol,  428  ():  (224-231).  [PMID:28601529]
13. Yamada M et al..  (2018)  Furin inhibitor protects against neuronal cell death induced by activated NMDA receptors..  Sci Rep,  8  ():  (5212).  [PMID:29581474]
14. Fleming T et al..  (2019)  Growth Hormone Neuroprotection Against Kainate Excitotoxicity in the Retina is Mediated by Notch/PTEN/Akt Signaling..  Invest Ophthalmol Vis Sci,  60  (14):  (4532-4547).  [PMID:31675424]
15. Zhai Z et al..  (2020)  Inflammasome Sensor NLRP1 Confers Acquired Drug Resistance to Temozolomide in Human Melanoma..  Cancers (Basel),  12  (9):  ().  [PMID:32899791]
16. Li K et al..  (2021)  M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way..  J Exp Clin Cancer Res,  40  ():  (325).  [PMID:34656164]
17. Zhao D et al..  (2017)  Notch Signaling Pathway Regulates Angiogenesis via Endothelial Cell in 3D Co-Culture Model..  J Cell Physiol,  232  (6):  (1548-1558).  [PMID:27861873]
18. Tan LS et al..  (2021)  Protocol for the generation of pancreatic and hepatic progenitors from human pluripotent stem cells for gene regulatory assays..  STAR Protoc,  2  (2):  (100471).  [PMID:33997805]
19. Lang C et al..  (2019)  Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes..  Cell Stem Cell,  24  ():  (93-106.e6).  [PMID:30503143]
20. Ngan SY et al..  (2022)  Stage-Specific Generation of Human Pluripotent Stem Cell Derived Lung Models to Measure CFTR Function..  Curr Protoc,  2  ():  (e341).  [PMID:35025140]
21. Capaccione KM & Pine SR.  (2013)  The Notch signaling pathway as a mediator of tumor survival..  Carcinogenesis,  34  (7):  (1420-30).  [PMID:23585460]
22. Wei H et al..  (2020)  Up-regulation of miR-139-5p protects diabetic mice from liver tissue damage and oxidative stress through inhibiting Notch signaling pathway..  Acta Biochim Biophys Sin (Shanghai),  52  (4):  (390-400).  [PMID:32293663]
23. Zakhari JS et al..  (2018)  Vasculogenic and angiogenic potential of adipose stromal vascular fraction cell populations in vitro..  In Vitro Cell Dev Biol Anim,  54  ():  (32-40).  [PMID:29197029]
24. Linaro D et al..  (2019)  Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits..  Neuron,  104  (5):  (972-986.e6).  [PMID:31761708]

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