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Chemical Structure| 1146699-66-2 Chemical Structure| 1146699-66-2

Structure of Avagacestat
CAS No.: 1146699-66-2

Chemical Structure| 1146699-66-2

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Avagacestat is an inhibitor of γ-secretase Aβ40 and Aβ42 with IC50s of 0.3 nM and 0.27 nM, respectively.

Synonyms: BMS-708163

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Product Details of Avagacestat

CAS No. :1146699-66-2
Formula : C20H17ClF4N4O4S
M.W : 520.89
SMILES Code : O=C(N)[C@H](N(CC1=CC=C(C2=NOC=N2)C=C1F)S(=O)(C3=CC=C(Cl)C=C3)=O)CCC(F)(F)F
Synonyms :
BMS-708163
MDL No. :MFCD13195458
InChI Key :XEAOPVUAMONVLA-QGZVFWFLSA-N
Pubchem ID :46883536

Safety of Avagacestat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
ANPP cells 100 nM 1 hour Through a large-scale photolabeling experiment, the binding site of the BMS-708163 probe on PS1 was determined, showing that the probe labeled the L282 site of PS1. PMC5516958
HeLa cells 2 µM 1 hour E2012-BPyne specifically labels PS1-NTF, and the labeling is competed in the presence of E2012 PMC3617273
H4-APP cells 1 µM 1 hour E2012-BPyne specifically labels PS1-NTF, and the labeling is competed in the presence of E2012 PMC3617273
ANP.24 cells 1 µM 1 hour E2012-BPyne preferentially labels active PS1-NTF over inactive full-length PS1 PMC3617273
PS1-G378E neurons 10 nM 20 days To evaluate the effect of BMS-708163 on the expression levels of RAB3A and SV2B proteins in PS1-G378E neurons, finding that RAB3A and SV2B protein levels increased by 2-fold and 3-fold, respectively PMC5027582
hepatic stellate cells 1 μM and 10 μM 24 hours To investigate the effect of testosterone on hepatic stellate cell activation in a KDM5B/KDM5C-dependent manner, results showed that testosterone significantly increased the expression of HSC activation markers in KDM5B/KDM5C-deficient cells. PMC11609386
LX2 cells 5 μM and 10 μM 24 hours Inhibited TGFβ-induced HSC activation and contractility, significantly reduced collagen I, α-SMA, and vimentin expression PMC4677309
RAW264.7 macrophages 10 μM 24 hours Inhibited M1 macrophage polarization, significantly reduced Hes1 expression and NO release PMC4677309
Mouse primary neurons 2 μM 4 days To investigate the effect of Avagacestat on PS1 levels, results showed that Avagacestat increased PS1 protein levels. PMC5948247
HeLa cells 20 nM To study the interaction of BMS-708163 probes with γ-secretase, the results showed that the labeling efficiency of PS1-NTF correlated with the IC50 values of the probes. PMC5516958
H4-8Sw cells 0.30 nM Inhibition of Aβ40 and Aβ42 formation PMC4007960

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice alcohol-induced liver fibrosis model Oral 10 mg/kg twice weekly for 4 weeks To evaluate the role of Notch signaling in alcohol-induced liver fibrosis, results showed that inhibiting Notch signaling significantly reduced liver fibrosis and abolished the effect of Kdm5b/Kdm5c loss. PMC11609386
Mice Tg2576 transgenic mice Oral 1-10 mg/kg Once daily for 8 days To compare the effects of GSIs and GSM on cognitive function in Tg2576 mice. The results showed that GSIs ameliorated cognitive deficits with acute dosing, but these effects disappeared after subchronic dosing and even impaired normal cognition. GSM-2 significantly ameliorated cognitive deficits without affecting normal cognition. PMC6621706
Rats Wistar rats Oral 40 mg/kg Once daily for 21 days To investigate the effect of Avagacestat on PS1 levels in rat brains, results showed that Avagacestat significantly increased PS1 protein levels in the brain. PMC5948247
Mice CCl4-induced liver fibrosis model intraperitoneal injection 10 mg/kg once daily for 2 days Significantly attenuated liver fibrosis, reduced HSC activation and inflammatory M1 macrophages, while upregulated suppressive M2 macrophages PMC4677309
Rats and dogs Wild-type rats and beagle dogs Oral 1, 3, 10, 30 mg/kg (rats); 2 mg/kg (dogs) Single dose Significantly reduced Aβ40 levels in brain, plasma, and cerebrospinal fluid PMC4007960

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00901498 Alzheimer's Disease ... More >> Healthy Less << Phase 1 Completed - United States, New Jersey ... More >> Mds Pharma Services (Us) Inc. Neptune, New Jersey, United States, 07753 Less <<
NCT00810147 Alzheimer's Disease Phase 2 Completed - -
NCT00828646 Healthy Phase 1 Completed - Japan ... More >> Local Institution Yokohama, Kanagawa, Japan, 2320064 Less <<
NCT00726726 Alzheimer Disease Phase 1 Completed - United States, New Jersey ... More >> Bristol-Myers Squibb Clinical Pharmacology Unit Hamilton, New Jersey, United States, 08690 Less <<
NCT01079819 Alzheimer's Disease Phase 1 Completed - United States, California ... More >> West Coast Clinical Trials, Llc Cypress, California, United States, 90630 California Clinical Trials Medical Group Glendale, California, United States, 91206 United States, New Jersey Iberica Clinical Research Center Eatontown, New Jersey, United States, 07724 Less <<
NCT00979316 Alzheimer Disease Phase 1 Completed - United States, Arizona ... More >> Mds Pharma Services (Us), Inc Tempe, Arizona, United States, 85283 Less <<
NCT01002079 Alzheimer Disease Phase 1 Completed - India ... More >> Local Institution Bangalore, India, 560100 Less <<
NCT01454115 Alzheimer's Disease Phase 1 Completed - -
NCT01057030 Alzheimer Disease Phase 1 Completed - United States, California ... More >> California Clinical Trials Medical Group Glendale, California, United States, 91206 Less <<
NCT00860275 Alzheimer Disease Phase 1 Completed - United States, Texas ... More >> Ppd Development, Lp Austin, Texas, United States, 78744 Less <<
NCT01039194 Alzheimer Disease Phase 1 Completed - United States, Maryland ... More >> Parexel International - Baltimore Epcu Baltimore, Maryland, United States, 21225 Less <<
NCT00890890 Alzheimer's Disease Phase 2 Terminated - -
NCT01042314 Alzheimer Disease Phase 1 Completed - United States, Maryland ... More >> Parexel International - Baltimore Epcu Baltimore, Maryland, United States, 21225 Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.60mL

1.92mL

0.96mL

19.20mL

3.84mL

1.92mL

References

 

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