AMG-8718 是一种有效的、选择性的和具有口服活性的BACE1抑制剂，对 BACE1 和 BACE2 的IC50值分别为 0.0007 和 0.005 μM。AMG-8718 显着降低 CSF 和大脑中的 Aβ40水平。

AMG-8718 is a potent, selective and orally active BACE1 inhibitor with IC 50 values of 0.0007, 0.005 μM for BACE1 and BACE2, respectively. AMG-8718 significantly decreases Aβ 40 levels in the CSF and brain [1].

AMG-8718 (compound 42) shows good stability in human and rat liver microsomes, hERG binding activity with an K i value of >10 μM [1].

AMG-8718 (compound 42) (10 mg/kg; p.o.)shows significantly decreases Aβ 40 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 (EC 50 ) 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) V dss (L/kg) t 1/2 (h) C max (μM) t max (h) % F plasma protein binding (F u ) 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 2 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 Aβ 40 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.

1215868-94-2

C25H19FN4O3

442.44

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years