| CAS NO: | 1361224-53-4 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 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 Code | CC#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 |
| 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 Vivo | AMG-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 model | Diet induced obese (DIO), ob/ob and db/db mice |
| Formulation & Dosage | Formulated 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. |
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