AMG-8718
AMG-8718 is a potent, selective and orally active BACE1 inhibitor with IC50 values of 0.0007, 0.005 µM for BACE1 and BACE2, respectively. AMG-8718 significantly decreases Aβ40 levels in the CSF and brain.
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- No. CAS: 1215868-94-2
- Fòrmula: C25H19FN4O3
- Peso molecular:442.44
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Verubecestat TFA -
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Verubecestat -
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LY2886721 -
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Lanabecestat -
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LY2811376 (Standard) -
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AZD3839 free base -
HY-100182R
BACE1-IN-1 (Standard) -
HY-109055
Elenbecestat -
HY-10133R
β-Secretase Inhibitor IV (Standard)
Actividad biológica
Descripciòn
IC50 & Target
[1]|
BACE1 0.0007 μM (IC50) |
BACE2 0.005 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
4.4 nM
Compound: 42, AMG-8718
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Inhibition of BACE1 in HEK293 cells assessed as Abeta40 level after overnight incubation by sandwich ELISA
Inhibition of BACE1 in HEK293 cells assessed as Abeta40 level after overnight incubation by sandwich ELISA
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[PMID: 25363711] |
In Vitro
AMG-8718 (compound 42) shows good stability in human and rat liver microsomes, hERG binding activity with an Ki value of >10 µM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
AMG-8718 (i.v. for 2 mg/kg or p.o. for 5 mg/kg) shows good bioavailability of 70%, 96%,101% for rats, beagle dog, monkey, respectively[1].
AMG-8718 (30 mg/kg for; p.o.) dose-dependent decreases in both CSF and brain Aβ levels at 4 h time points with 50% Aβ reduction (EC50) values of 18 and 67 nM for CSF and brain respectively in rats[1].
AMG-8718 (2.5, 8, 16 mg/kg; i.v.; a series of three 30 min infusions) shows high unbound plasma concentrations with 0.298, 1.70, 3.62 µM at the end of each infusion in chloralose-anesthetized dogs[1].
Pharmacokinetic Parameters ofAMG-8718 in rats, beagle dog, cynomolgus monkey[1].
| species | Cl (L/h/kg) | Vdss(L/kg) | t1/2(h) | Cmax (µM) | tmax(h) | % F | plasma protein binding (Fu) | |
| i.v. | p.o. | |||||||
| rat | 0.33 | 1.1 | 4.8 | 3.8 | 1.7 | 70 | 0.013 | |
| beagle dog | 0.26 | 1.6 | 5.2 | 8.1 | 1.0 | 96 | 0.038 | |
| monkey | 0.61 | 2.2 | 7.7 | 6.1 | 1.7 | 101 | 0.054 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Sprague-Dawley rats[1]
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Dosage:10 mg/kg
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Administration:Oral gavage
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Result:Significantly decreased Aβ40 levels in the CSF at the 4 h time point at 69%, produced a robust response in the brain with 48% reduction of Aβ40 levels.
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Animal Model:Rats, beagle dog, monkey[1]
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Dosage:2, 5 mg/kg
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Administration:I.v. for 2 mg/kg or p.o. for 5 mg/kg
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Result:Showed moderate total clearance, moderate Vdss, and half-lives of ca. 5-8 h across all three species, and bioavailability was high (70–101%).
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Animal Model:Rats[1]
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Dosage:30 mg/kg
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Administration:P.o.
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Result:Demonstrated dose-dependent decreases in both CSF and brain Aβ levels at 4 h and 8 h time points.
Chemical Information
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No. CAS 1215868-94-2
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Peso molecular 442.44
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Fòrmula C25H19FN4O3
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SMILES
NC(OC1)=N[C@]1(C2=CC(C#CC3(C)COC3)=CN=C2O4)C5=C4C=CC(C6=CC=CN=C6F)=C5
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
AMG-8718 Related Classifications
HY-12938 Related Classifications
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