AMG 8718

Modify Date: 2024-02-22 15:09:17

AMG 8718 Structure
AMG 8718 structure
Common Name AMG 8718
CAS Number 1215868-94-2 Molecular Weight 442.442
Density 1.4±0.1 g/cm3 Boiling Point 673.7±65.0 °C at 760 mmHg
Molecular Formula C25H19FN4O3 Melting Point N/A
MSDS N/A Flash Point 361.2±34.3 °C

 Use of 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[1].

 Names

Name (5S)-7-(2-Fluoro-3-pyridinyl)-3-[(3-methyl-3-oxetanyl)ethynyl]spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine
Synonym More Synonyms

 AMG 8718 Biological Activity

Description 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[1].
Related Catalog
Target

BACE1:0.0007 μM (IC50)

BACE2:0.005 μM (IC50)

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].
In Vivo AMG-8718 (compound 42) (10 mg/kg; p.o.)shows significantly decreases Aβ40 levels in the CSF and brain[1]. 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 0.0542 mg/kg i.v.; rats (DMSO), dog (1% Tween80/2% HMPC/97% water at pH = 4), cynomolgus monkey (25% HBC/75% water at pH = 4); 5 mg/kg p.o. (1% Tween80/2% HMPC/97% water at pH = 2)[1]. Animal Model: Male Sprague-Dawley rats[1] Dosage: 10 mg/kg Administration: Oral gavage 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. Animal Model: Rats, beagle dog, monkey[1] Dosage: 2, 5 mg/kg Administration: I.v. for 2 mg/kg or p.o. for 5 mg/kg 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%). Animal Model: Rats[1] Dosage: 30 mg/kg Administration: P.o. Result: Demonstrated dose-dependent decreases in both CSF and brain Aβ levels at 4 h and 8 h time points.
References

[1]. Dineen TA,et al. Inhibitors of β-site amyloid precursor protein cleaving enzyme (BACE1): identification of (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine (AMG-8718). J Med Chem. 2014 Dec 11;57(23):9811-31.

 Chemical & Physical Properties

Density 1.4±0.1 g/cm3
Boiling Point 673.7±65.0 °C at 760 mmHg
Molecular Formula C25H19FN4O3
Molecular Weight 442.442
Flash Point 361.2±34.3 °C
Exact Mass 442.144104
LogP 2.47
Vapour Pressure 0.0±2.1 mmHg at 25°C
Index of Refraction 1.699

 Synonyms

(5S)-7-(2-Fluoro-3-pyridinyl)-3-[(3-methyl-3-oxetanyl)ethynyl]spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine
(5s)-7-(2-Fluoropyridin-3-Yl)-3-[(3-Methyloxetan-3-Yl)ethynyl]spiro[chromeno[2,3-B]pyridine-5,4'-[1,3]oxazol]-2'-Amine
Spiro[5H--1benzopyrano[2,3-b]pyridine-5,4'(5'H)-oxazol]-2'-amine, 7-(2-fluoro-3-pyridinyl)-3-[2-(3-methyl-3-oxetanyl)ethynyl]-, (5S)-
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