产品
编 号：F075602
分子式：C25H19FN4O3
分子量：442.44
分子式：C25H19FN4O3
分子量：442.44
产品类型
规格
价格
是否有货
结构图
CAS No: 1215868-94-2
产品详情
生物活性：
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.
体内研究：
AMG-8718 (compound 42) (10 mg/kg; p.o.)shows significantly decreases Aβ40 levels in the CSF and brain.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.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.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.Pharmacokinetic Parameters ofAMG-8718 in rats, beagle dog, cynomolgus monkey.speciesCl (L/h/kg)Vdss(L/kg) t1/2(h) Cmax (μM)tmax(h)% Fplasma protein binding (Fu)
i.v.p.o.
rat0.331.14.83.81.7700.013
beagle dog0.261.65.28.11.0960.038
monkey0.612.27.76.11.71010.054
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).Animal Model:Male Sprague-Dawley rats
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
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
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.
体外研究：
AMG-8718 (compound 42) shows good stability in human and rat liver microsomes, hERG binding activity with an Ki value of >10 μM.
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.
体内研究：
AMG-8718 (compound 42) (10 mg/kg; p.o.)shows significantly decreases Aβ40 levels in the CSF and brain.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.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.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.Pharmacokinetic Parameters ofAMG-8718 in rats, beagle dog, cynomolgus monkey.speciesCl (L/h/kg)Vdss(L/kg) t1/2(h) Cmax (μM)tmax(h)% Fplasma protein binding (Fu)
i.v.p.o.
rat0.331.14.83.81.7700.013
beagle dog0.261.65.28.11.0960.038
monkey0.612.27.76.11.71010.054
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).Animal Model:Male Sprague-Dawley rats
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
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
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.
体外研究：
AMG-8718 (compound 42) shows good stability in human and rat liver microsomes, hERG binding activity with an Ki value of >10 μM.
产品资料
Copyright©2015-2024 沪ICP备2022026524号-1
沪公网安备