[CAS NO. 1361224-53-4] AMG-3969
PRODUCTS SPECIFICATIONS [1361224-53-4]
DESCRIPTION [1361224-53-4]
Overview
| MDL | MFCD28386194 |
|---|---|
| Molecular Weight | 522.46 |
| Molecular Formula | C21H20F6N4O3S |
| SMILES | 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 |
1 Publications Citing Use of MCE
Summary
AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction ( GK-GKRP ) disruptor with an IC 50 of 4 nM.
IC50 & Target
IC50: 4 nM (GK-GKRP) [1]
In Vitro
AMG-3969 exhibits potent cellular activity with an EC 50 of 0.202 μM and IC 50 of 4 nM [1] , [2] . It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes) [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 191.40 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9140 mL | 9.5701 mL | 19.1402 mL |
| 5 mM | 0.3828 mL | 1.9140 mL | 3.8280 mL |
| 10 mM | 0.1914 mL | 0.9570 mL | 1.9140 mL |
References
- [1] Lloyd DJ, et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature. 2013 Dec 19;504(7480):437-40.
- [2] Nishimura N, et al. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N'-arylpiperazine series. J Med Chem. 2014 Apr 10;5
- [3] St Jean DJ Jr, et al. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles. J Med Chem. 2014 Jan 23;57(2):325-38.