Begacestat
Based on 1 Customer Validation
Begacestat (GSI-953) is a selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase (IC50Aβ40=15 nM) for the treatment of Alzheimer's disease.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.05%
- No. CAS: 769169-27-9
- Fòrmula: C9H8ClF6NO3S2
- Peso molecular:391.74
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
IC50: 15 nM (Aβ40)[1].
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | ED50 |
350 nM
Compound: 42
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Inhibition of gamma-secretase in CHO cells assessed expressing NotchdeltaE assessed as inhibition of notch cleavage after overnight incubation by luciferase reporter gene assay
Inhibition of gamma-secretase in CHO cells assessed expressing NotchdeltaE assessed as inhibition of notch cleavage after overnight incubation by luciferase reporter gene assay
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[PMID: 23713656] |
| CHO | ED50 |
7.8 nM
Compound: 42
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Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA
Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA
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[PMID: 23713656] |
| CHO | IC50 |
14.8 nM
Compound: 16; GSI-953
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Inhibition of gamma secretase (unknown origin) mediated APP cleavage in CHO cells expressing APP Swedish KM/NL mutant assessed as reduction in amyloid beta 40 after 24 hrs by sandwich ELISA
Inhibition of gamma secretase (unknown origin) mediated APP cleavage in CHO cells expressing APP Swedish KM/NL mutant assessed as reduction in amyloid beta 40 after 24 hrs by sandwich ELISA
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[PMID: 27045975] |
| CHO | IC50 |
15 nM
Compound: 5, begacestat
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Inhibition of gamma-secretase expressed in CHO cells expressing human recombinant APP assessed as amyloid beta40 aggregation
Inhibition of gamma-secretase expressed in CHO cells expressing human recombinant APP assessed as amyloid beta40 aggregation
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[PMID: 19012391] |
| CHO | IC50 |
353 nM
Compound: GSI-953
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Inhibition of gamma-secretase in CHO cells after overnight incubation by luciferase reporter gene assay
Inhibition of gamma-secretase in CHO cells after overnight incubation by luciferase reporter gene assay
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[PMID: 23312944] |
| HEK293 | ED50 |
7.8 nM
Compound: GSI-953
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Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis
Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis
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[PMID: 23312944] |
| IMR-32 | IC50 |
1.6 nM
Compound: GSI-953
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Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA
Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA
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[PMID: 23312944] |
| IMR-32 | IC50 |
10.5 nM
Compound: GSI-953
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Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA
Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA
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[PMID: 23312944] |
| SH-SY5Y | IC50 |
15 nM
Compound: 62, Begacestat
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Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells
Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells
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[PMID: 19694467] |
| SH-SY5Y | IC50 |
8 nM
Compound: 62, Begacestat
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Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay
Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay
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[PMID: 19694467] |
Begacestat (GSI-953: 0, 2.5, 5, or 10 mg/kg, oral gavage, 3 h) results in a dose-dependent reversal of contextual fear conditioning deficits when compound is orally administered 3 h before training. Significant deficits are observed after treatment with 2.5 mg/kg Begacestat, and there is some reversal of this at 5 mg/kg and full reversal at 10 mg/kg compared with vehicle-dosed Tg2576 mice[2].
A dosage-related trend of slightly lower percentages of SP CD4+ cells in males at all dosages (SP CD4+ cells=~11% in controls compared with ~7% to ~9% in Begacestat-dosed animals) and females at 2000 mg/kg/day (SP CD4+ cells=~10% in controls compared with ~8% in Begacestat-dosed animals) is observed[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Tg2576 mice[2]
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Dosage:0, 2.5, 5, or 10 mg/kg
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Administration:Oral gavage for two consecutive days
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Result:Resulted in a dose-dependent reversal of contextual fear conditioning deficits when compound is orally administered 3 h before training.
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Animal Model:Sprague-Dawley rats[2]
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Dosage:0, 200, 600, or 2000 mg/kg/day for 10 (5 males/group and 5 females at 600 mg/kg/day) or 28 (10/sex/group) consecutive days
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Administration:P.O. for 10 (5 males/group and 5 females at 600 mg/kg/day) or 28 (10/sex/group) consecutive days.
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Result:A dosage-related trend of slightly lower percentages of SP CD4+ cells in males at all dosages and females at 2000 mg/kg/day was observed.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 769169-27-9
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Appearance Solid
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Peso molecular 391.74
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Fòrmula C9H8ClF6NO3S2
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Color White to off-white
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SMILES
FC(F)(F)C([C@H](NS(=O)(C1=CC=C(Cl)S1)=O)CO)C(F)(F)F
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Synonyms
GSI-953
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 50 mg/mL (127.64 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.38 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.38 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (276 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Mayer SC, et al. Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease. J Med Chem. 2008 Dec 11;51(23):7348-51. [Content Brief]
[2]. Martone RL, et al. Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease. J Pharmacol Exp Ther. 2009 Nov;331(2):598-608. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.5527 mL | 12.7636 mL | 25.5271 mL | 63.8178 mL |
| 5 mM | 0.5105 mL | 2.5527 mL | 5.1054 mL | 12.7636 mL | |
| 10 mM | 0.2553 mL | 1.2764 mL | 2.5527 mL | 6.3818 mL | |
| 15 mM | 0.1702 mL | 0.8509 mL | 1.7018 mL | 4.2545 mL | |
| 20 mM | 0.1276 mL | 0.6382 mL | 1.2764 mL | 3.1909 mL | |
| 25 mM | 0.1021 mL | 0.5105 mL | 1.0211 mL | 2.5527 mL | |
| 30 mM | 0.0851 mL | 0.4255 mL | 0.8509 mL | 2.1273 mL | |
| 40 mM | 0.0638 mL | 0.3191 mL | 0.6382 mL | 1.5954 mL | |
| 50 mM | 0.0511 mL | 0.2553 mL | 0.5105 mL | 1.2764 mL | |
| 60 mM | 0.0425 mL | 0.2127 mL | 0.4255 mL | 1.0636 mL | |
| 80 mM | 0.0319 mL | 0.1595 mL | 0.3191 mL | 0.7977 mL | |
| 100 mM | 0.0255 mL | 0.1276 mL | 0.2553 mL | 0.6382 mL |
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