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AMG-3969
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AMG-3969图片
CAS NO:1361224-53-4
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 522.46
Formula C21H20F6N4O3S
CAS No. 1361224-53-4
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM in DMSO
Water: <1 mg/mL
Ethanol:
SMILES CodeCC#C[C@@H]1N(C2=CC=C(C(C(F)(F)F)(O)C(F)(F)F)C=C2)CCN(S(=O)(C3=CN=C(N)C=C3)=O)C1
Synonyms AMG-3969; AMG 3969; AMG3969
实验参考方法
In Vitro

In vitro activity: AMG-3969 is a potent, novel and metabolically stable disruptor of glucokinase-glucokinase regulatory protein interaction (GK-GKRP) with IC50 of 4 nM. AMG-3969 exhibits potent cellular activity with an EC50 of 0.202 μM and IC50 of 4 nM. It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes). When administered to db/db mice, AMG-3969 demonstrated a robust pharmacodynamic response (GK translocation) as well as statistically significant dose-dependent reductions in fed blood glucose levels. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus. A


Kinase Assay: MG-3969 exhibits potent cellular activity with an EC50 of 0.202 μM and IC50 of 4 nM.


Cell Assay: MG-3969 exhibits potent cellular activity with an EC50 of 0.202 μM and IC50 of 4 nM. It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes)

In VivoAMG-3969 (100 mg/kg) demonstrates significant reductions in blood glucose with robust efficacy (56% reduction) observed at the 8 h time point. AMG-3969 demonstrates dose-dependent efficacy in three models of diabetes: diet induced obese (DIO), ob/ob and db/db mice; however, AMG-3969 is ineffective in lowering blood glucose in normoglycaemic C57BL/6 (B6) mice. AMG-3969 is highly effective in promoting carbohydrate substrate. AMG-3969 exhibits extended changes to carbohydrate oxidation as observed by increased respiratory exchange ratio into the next night and day after a single dose. AMG-3969 has good in vivo pharmacokinetic (PK) properties in rats (75%) and significantly lowers blood glucose levels in a dose-dependent manner db/db mice.
Animal modelDiet induced obese (DIO), ob/ob and db/db mice
Formulation & DosageFormulated in 2% hydroxypropyl methycellulose, 1% Tween 80, pH 2.2 adjusted with MSA; 10, 30, 100 mg/kg; P.O.
References Nature. 2013 Dec 19;504(7480):437-40; J Med Chem. 2014 Apr 10; 57(7):3094-116; J Med Chem. 2014 Jan 23;57(2):325-38.