| Chemical Properties | Back Directory | [Boiling point ]
648.8±65.0 °C(Predicted) | [density ]
1.56±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C(protect from light) | [solubility ]
DMSO:100.0(Max Conc. mg/mL);191.4(Max Conc. mM) | [form ]
Solid | [pka]
10.12±0.15(Predicted) | [color ]
White to off-white |
| Questions and Answers (Q&A) | Back Directory | [Description]
AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor. Itcan strongly boost the dissociation of the GK-GKRP complex and promote GK translocation in-vivo. In rodent model of diabetes, AMG-3969 reduces blood glucose levels without affecting euglycemic animals. It is a promising drug for the treatment of type II diabetes through lowering blood glucose levels with reduced potential for hypoglycaemic risk.
| [References]
Lloyd, David J., et al. "Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors." Nature 504.7480(2013):437-40.
Bourbeau, M. P., et al. "Nonracemic synthesis of GK-GKRP disruptor AMG-3969. " Synfacts 79.8(2014):3684.
http://www.metonchem.com/products/amg-3969-cas1361224-53-4/
|
| Hazard Information | Back Directory | [Uses]
AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM. | [in vivo]
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[1]. AMG-3969 (100 mg/kg) demonstrates significant reductions in blood glucose with robust efficacy (56% reduction) observed at the 8 h time point[2]. 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[3]. |
|
|