Cell permeable, potent, selective, non-transition state and non-competitive inhibitor of γ-secretase (IC50=0.3nM for total β-amyloid) and Notch processing, which ceases cell differentiation. At higher concentrations (20-400µM), only weakly affects the presenilase activity. Activity tested!
Product Details
| Alternative Name: | (2S)-2-{[(3,5-Difluorophenyl)acetyl]amino}-N-[(3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]propanamide, γ-Secretase Inhibitor, GSI |
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| Formula: | C27H24F2N4O3 |
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| MW: | 490.5 |
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| CAS: | 209986-17-4 |
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| Purity: | ≥95% (HPLC) |
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| Appearance: | White to off-white powder. |
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| Solubility: | Soluble in DMSO. |
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| Shipping: | Ambient |
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| Short Term Storage: | +4°C |
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| Long Term Storage: | -20°C |
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| Handling: | Keep under inert gas. |
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| Regulatory Status: | RUO - Research Use Only |
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Product Literature References
Leukemia-specific delivery of mutant NOTCH1 targeted therapy.: G. Roti, et al.; J. Exp. Med.
215, 197 (2018),
Abstract;
Full Text
A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia: J. Robles-Valero, et al.; Cancer Cell
32, 608 (2017),
Abstract;
Full Text
Mechanism of BMP9 promotes growth of osteosarcoma mediated by the Notch signaling pathway: P. Liu, et al.; Oncol. Lett.
11, 1367 (2016),
Application(s): Notch Inhibition in Cell Culture,
Abstract;
Full Text
Necrosis- and apoptosis-related Met cleavages have divergent functional consequences: R. Montagne, et al.; Cell Death Dis.
6, e1769 (2015),
Application(s): Cell Culture,
Abstract;
Full Text
Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand: I.M. Kim, et al.; Circ. Res.
106, 1233 (2010),
Abstract;
Down-regulation of the met receptor tyrosine kinase by presenilin-dependent regulated intramembrane proteolysis: B. Foveau, et al.; Mol. Biol. Cell
20, 2495 (2009),
Abstract;
Synaptic activity prompts gamma-secretase-mediated cleavage of EphA4 and dendritic spine formation: E. Inoue, et al.; J. Cell. Biol.
185, 551 (2009),
Abstract;
Determination of guinea-pig cortical gamma-secretase activity ex vivo following the systemic administration of a gamma-secretase inhibitor: S. Grimwood, et al.; Neuropharmacology
48, 1002 (2005),
Abstract;
Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia: A.P. Weng, et al.; Science
306, 269 (2004),
Abstract;
Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein: G. Zhao, et al.; J. Biol. Chem.
279, 50647 (2004),
Abstract;
Full Text
Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule: Z. Zou, et al.; J. Biol. Chem.
279, 34302 (2004),
Abstract;
Full Text
Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria: C.A. Hansson, et al.; J. Biol. Chem.
279, 51654 (2004),
Abstract;
Full Text
Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44: D. Murakami, et al.; Oncogene
22, 1511 (2003),
Abstract;
Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor: K.M. Jung, et al.; J. Biol. Chem.
278, 42161 (2003),
Abstract;
Full Text
aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation: R. Francis, et al.; Dev. Cell
3, 85 (2002),
Abstract;
Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines: G. Tian, et al.; J. Biol. Chem.
277, 31499 (2002),
Abstract;
Full Text
Presenilin-dependent gamma-secretase-like intramembrane cleavage of ErbB4: H.J. Lee, et al.; J. Biol. Chem.
277, 6318 (2002),
Abstract;
Full Text
gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase: C.Y. Ni, et al.; Science
294, 2179 (2001),
Abstract;
Pharmacological knock-down of the presenilin 1 heterodimer by a novel gamma -secretase inhibitor: implications for presenilin biology: D. Beher, et al.; J. Biol. Chem.
276, 45394 (2001),
Abstract;
Full Text
Presenilin-dependent gamma-secretase activity modulates thymocyte development: P. Doerfler, et al.; PNAS
98, 9312 (2001),
Abstract;
Full Text
Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors: D. Seiffert, et al.; J. Biol. Chem.
275, 34086 (2000),
Abstract;
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