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AMG-3969 1361224-53-4
AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM.
| Cas No. | 1361224-53-4 |
Canonical 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 |
Formula | C21H20F6N4O3S |
M.Wt | 522.46 |
Solubility | DMSO : ≥ 100 mg/mL (191.40 mM) |
Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. |
| To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
AMG-3969 exhibits potent cellular activity with an EC50 of 0.202 uM and IC50 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].
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].
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;57(7):3094-116.
[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.
For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.