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BMS-708163

Cat. No. M1947
BMS-708163 Structure
Synonym:

Avagacestat

Size Price Availability Quantity
10mg USD 280 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

BMS-708163 (Avagacestat) is a potent, selective γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, respectively. BMS-708163 binds directly to the presenilin-1 N-terminal fragment and that binding can be challenged by other pan-GSIs, but not by γ-secretase modulators. BMS-708163 blocks the binding of four different active site-directed GSI photoaffinity probes. Administration of a single dose of 200 or 400 mg of BMS-708163 resulted in a marked decrease in CSF Aβ(1-38), Aβ(1-40) and Aβ(1-42) concentrations vs placebo; with smaller decreases observed in the 50 mg dose group. BMS-708163 (Avagacestat) was quickly absorbed into the systemic circulation, with a mean time to reach maximum plasma concentration (t(max)) of approximately 1-2 h, and a CSF t(max) of approximately 3 h. BMS-708163 is 190-fold more selective for APP than Notch, having an IC50 of 58 nM for Notch.

Protocol
Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time
Animal Experiment
Animal models Harlan Sprague Dawley rat or ATM-405-142K9 naive II dog
Formulation 99% PEG-400, 1% Tween-80 (rat),or 94% labrafil-1944, 5% ethanol, 1% Tween-80 (dog)
Dosages 10 mg/kg (rat) or 2.5 mg/kg (dog)
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 520.88
Formula C20H17ClF4N4O4S
CAS Number 1146699-66-2
Purity >99%
Solubility DMSO 100 mg/mL
Storage at -20°C
References

Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor.
Gillman KW, et al. ACS Med Chem Lett. 2010 Mar 22;1(3):120-4. PMID: 24900185.

Effects of Single Doses of Avagacestat (BMS-708163) on Cerebrospinal Fluid Aβ Levels in Healthy Young Men.
Tong G, et al. Clin Drug Investig. 2012 Sep 14. PMID: 23018285.

BMS-708,163 targets presenilin and lacks notch-sparing activity.
Crump CJ, et al. Biochemistry. 2012 Sep 18;51(37):7209-11. PMID: 22931393.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: BMS-708163, Avagacestat supplier, Gamma-secretase, inhibitors

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