Begacestat (Synonyms: GSI-953)

Name: Begacestat
Brand: MedChemExpress
SKU: HY-14175
Rating: 4.5 (1 reviews)

Cat. No.: HY-14175 Purity: 99.29%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

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.

For research use only. We do not sell to patients.

Begacestat Chemical Structure

CAS No. : 769169-27-9

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 110	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 110	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 128	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 205	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 410	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 656	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1050	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

or Bulk Inquiry

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 1 publication(s) in Google Scholar

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity
Purity & Documentation
References
Customer Review

Description

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^[1].

IC₅₀ & Target

IC50: 15 nM (Aβ₄₀)^[1].

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC₅₀	14.8 nM Compound: 16; GSI-953	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	[PMID: 27045975]
CHO	ED₅₀	350 nM Compound: 42	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	[PMID: 23713656]
CHO	IC₅₀	353 nM Compound: GSI-953	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	[PMID: 23312944]
CHO	ED₅₀	7.8 nM Compound: 42	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	[PMID: 23713656]
HEK293	ED₅₀	7.8 nM Compound: GSI-953	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	[PMID: 23312944]
IMR-32	IC₅₀	1.6 nM Compound: GSI-953	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	[PMID: 23312944]
IMR-32	IC₅₀	10.5 nM Compound: GSI-953	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	[PMID: 23312944]
SH-SY5Y	IC₅₀	8 nM Compound: 62, Begacestat	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	[PMID: 19694467]

In Vivo

Begacestat (5 mg/kg, p.o. in mice) treatment for 4 h significantly reduces the Aβ₄₀ and Aβ₄₂ in brain (37% lowering of brain Aβ₄₀ and 25% lowering of Aβ₄₀ observed)^[1].
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.

Animal Model:	Tg2576 mice^[2]
Dosage:	0, 2.5, 5, or 10 mg/kg
Administration:	Oral gavage for two consecutive days
Result:	Resulted in a dose-dependent reversal of contextual fear conditioning deficits when compound is orally administered 3 h before training.

Animal Model:	Sprague-Dawley rats^[2]
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
Administration:	P.O. for 10 (5 males/group and 5 females at 600 mg/kg/day) or 28 (10/sex/group) consecutive days.
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.

Clinical Trial

Molecular Weight

391.74

Formula

C₉H₈ClF₆NO₃S₂

CAS No.

769169-27-9

Appearance

Solid

Color

White to off-white

SMILES

FC(F)(F)C([C@H](NS(=O)(C1=CC=C(Cl)S1)=O)CO)C(F)(F)F

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.5527 mL	12.7636 mL	25.5271 mL
5 mM	0.5105 mL	2.5527 mL	5.1054 mL
10 mM	0.2553 mL	1.2764 mL	2.5527 mL

View the 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.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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.

Protocol 1

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.
Protocol 2

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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.38 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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.

Purity & Documentation

Purity: 99.29%

Select Batch:

Data Sheet (276 KB) SDS (251 KB)

COA (250 KB) LCMS (84 KB)

Handling Instructions (2659 KB)

References

[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

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

Begacestat Related Classifications

Neurological Disease

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Begacestat769169-27-9GSI-953GSI953GSI 953γ-secretaseGamma secretaseInhibitorinhibitorinhibit

Your Recently Viewed Products:

Product Name

Salutation

Applicant Name *

Email Address *

Phone Number *

Organization Name *

Department *

Requested quantity *

Country or Region *

Remarks

Product Name

Lot #

Applicant Name *

Email Address *

Phone Number

Department *

Organization Name *

Country or Region *

Remarks

Name
Email *

	Sorry, but the email address you supplied was invalid.

Begacestat (Synonyms: GSI-953)

Customer Review

Begacestat Related Antibodies

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Purity & Documentation

References

Customer Review

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

Begacestat Related Classifications

Keywords:

Your Recently Viewed Products:

Customer Review

Request for HNMR Report

SAFETY DATA SHEET (SDS)

Request for HNMR Report