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Avagacestat (BMS-708163)

Name: Avagacestat (BMS-708163)
Brand: Selleck Chemicals
SKU: S1262
Rating: 5 (22 reviews)

Catalog No.S1262 Purity:99.63%

Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.

Avagacestat (BMS-708163) Chemical Structure

CAS No. 1146699-66-2

Purity & Quality Control

Batch: Purity: 99.63%

99.63

Avagacestat (BMS-708163) Related Products

Related Targets	gamma-secretase	Click to Expand
Related Products	DAPT RO4929097 DBZ (Dibenzazepine) LY411575 MK-0752 Semagacestat (LY450139) Nirogacestat (PF-03084014) MDL-28170 L-685,458	Click to Expand
Related Compound Libraries	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Protease Inhibitor Library Ubiquitination Compound Library	Click to Expand

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
human IMR32 cell	Function assay	2 h	Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA, IC50=0.13 nM	23312944
human H4 cells	Function assay		Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cells expressing human APP swedish mutant, IC50=0.225 μM	22420884
HEK293 cells	Function assay		Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis, IC50=1.2 nM	23312944
CHO cells	Function assay		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, ED50=1.2 nM	23713656
human IMR32 cell	Function assay	2 h	Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA, IC50=1.5 nM	23312944
human 786-0 cell	Growth inhibition assay		Inhibition of human 786-0 cell growth in a cell viability assay, IC50=0.32173 μM	SANGER
human NCI-H810 cell	Growth inhibition assay		Inhibition of human NCI-H810 cell growth in a cell viability assay, IC50=0.42598 μM	SANGER
human IGR-1 cell	Growth inhibition assay		Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=1.04778 μM	SANGER
human SK-MEL-3 cell	Growth inhibition assay		Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=1.49922 μM	SANGER
human HT-1080 cell	Growth inhibition assay		Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=2.48764 μM	SANGER
human NCI-H23 cell	Growth inhibition assay		Inhibition of human NCI-H23 cell growth in a cell viability assay, IC50=3.9322 μM	SANGER
human Calu-6 cell	Growth inhibition assay		Inhibition of human Calu-6 cell growth in a cell viability assay, IC50=4.96014 μM	SANGER
human CAPAN-1 cell	Growth inhibition assay		Inhibition of human CAPAN-1 cell growth in a cell viability assay, IC50=5.17886 μM	SANGER
human COLO-668 cell	Growth inhibition assay		Inhibition of human COLO-668 cell growth in a cell viability assay, IC50=5.40221 μM	SANGER
human TE-6 cell	Growth inhibition assay		Inhibition of human TE-6 cell growth in a cell viability assay, IC50=6.19082 μM	SANGER
human LCLC-97TM1 cell	Growth inhibition assay		Inhibition of human LCLC-97TM1 cell growth in a cell viability assay, IC50=10.0886 μM	SANGER
human CAS-1 cell	Growth inhibition assay		Inhibition of human CAS-1 cell growth in a cell viability assay, IC50=13.671 μM	SANGER
human RPMI-2650 cell	Growth inhibition assay		Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=13.8124 μM	SANGER
human MDA-MB-157 cell	Growth inhibition assay		Inhibition of human MDA-MB-157 cell growth in a cell viability assay, IC50=14.2431 μM	SANGER
human KINGS-1 cell	Growth inhibition assay		Inhibition of human KINGS-1 cell growth in a cell viability assay, IC50=14.3762 μM	SANGER
human BB49-HNC cell	Growth inhibition assay		Inhibition of human BB49-HNC cell growth in a cell viability assay, IC50=14.4138 μM	SANGER
human SK-UT-1 cell	Growth inhibition assay		Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=14.6882 μM	SANGER
human EW-11 cell	Growth inhibition assay		Inhibition of human EW-11 cell growth in a cell viability assay, IC50=14.8832 μM	SANGER
human D-502MG cell	Growth inhibition assay		Inhibition of human D-502MG cell growth in a cell viability assay, IC50=14.9034 μM	SANGER
human MMAC-SF cell	Growth inhibition assay		Inhibition of human MMAC-SF cell growth in a cell viability assay, IC50=15.0833 μM	SANGER
human NCI-H1648 cell	Growth inhibition assay		Inhibition of human NCI-H1648 cell growth in a cell viability assay, IC50=15.778 μM	SANGER
human NCI-H292 cell	Growth inhibition assay		Inhibition of human NCI-H292 cell growth in a cell viability assay, IC50=15.8806 μM	SANGER
human NMC-G1 cell	Growth inhibition assay		Inhibition of human NMC-G1 cell growth in a cell viability assay, IC50=16.6293 μM	SANGER
human SAS cell	Growth inhibition assay		Inhibition of human SAS cell growth in a cell viability assay, IC50=17.7812 μM	SANGER
human HCT-116 cell	Growth inhibition assay		Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=18.7965 μM	SANGER
human SBC-5 cell	Growth inhibition assay		Inhibition of human SBC-5 cell growth in a cell viability assay, IC50=19.03 μM	SANGER
Click to View More Cell Line Experimental Data

Biological Activity

Description

Features

Appears to be more “notch sparing” than semagacestat (LY450139).

Targets

Aβ42 ^[1] (in H4-8Sw cells)	Aβ40 ^[1] (in H4-8Sw cells)
0.27 nM	0.3 nM

In vitro
In vitro	BMS-708163 exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value. ^[1]

In Vivo
In vivo	Oral administration of BMS-708163 significantly reduces Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs. BMS-708163 has no dose-limiting effects in dogs (3 mg/kg during 6 months), with a high brain to plasma ratio (2.4). ^[1]
Animal Research	Animal Models	Female Harlan Sprague-Dawley rats or ATM-405-142K9 with 7- 10 month old Na?ve, grade II beagles
	Dosages	10 mg/kg (rats) or 2.5 mg/kg (dogs)
	Administration	Dosed daily by oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT01002079	Completed	Alzheimer Disease	Bristol-Myers Squibb\|PRA Health Sciences	August 2010	Phase 1
NCT01057030	Completed	Alzheimer Disease	Bristol-Myers Squibb	March 2010	Phase 1
NCT01042314	Completed	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT01039194	Completed	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT00979316	Completed	Alzheimer Disease	Bristol-Myers Squibb	September 2009	Phase 1
NCT00890890	Terminated	Alzheimer''s Disease	Bristol-Myers Squibb	May 2009	Phase 2

References

[1] Gillman KW, et al. Med Chem Lett, 2010, 1 (3), 120–124.

Chemical Information & Solubility

Molecular Weight	520.88	Formula	C₂₀H₁₇ClF₄N₄O₄S
CAS No.	1146699-66-2	SDF	Download Avagacestat (BMS-708163) SDF
Smiles	C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 104 mg/mL ( (199.66 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.650mg/ml (3.17mM)	Taking the 1 mL working solution as an example, add 50 μL of 33 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

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