Home Proteases Secretase inhibitor - Beta Amyloid inhibitor - Notch inhibitor Avagacestat (BMS-708163) For research use only.

Avagacestat (BMS-708163)

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

Avagacestat (BMS-708163) Chemical Structure

CAS No. 1146699-66-2

Purity & Quality Control

Avagacestat (BMS-708163) Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation 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 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.
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
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

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)

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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

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