| Bioactivity | AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM. | ||||||||||||
| Target | IC50: 4 nM (GK-GKRP) | ||||||||||||
| Invitro | AMG-3969 exhibits potent cellular activity with an EC50 of 0.202 μM 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]. | ||||||||||||
| 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]. | ||||||||||||
| Name | AMG-3969 | ||||||||||||
| CAS | 1361224-53-4 | ||||||||||||
| Formula | C21H20F6N4O3S | ||||||||||||
| Molar Mass | 522.46 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |
AMG-3969
CAS: 1361224-53-4 F: C21H20F6N4O3S W: 522.46
AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM.
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