AMG-3969 demonstrates strong cellular activity, with an EC50 of 0.202 μM and IC50 of 4 nM [1]. It effectively counteracts GKRP's inhibition of GK activity and facilitates GK translocation in vitro (using isolated hepatocytes) [3].
体内研究
AMG-3969 demonstrates favorablein vivo pharmacokinetic (PK) properties in rats (75%) and effectively reduces blood glucose levels in db/db mice in a dose-dependent manner [1].
AMG-3969 (100mg/kg) shows a significant hypoglycemic effect and a strong effect (56% reduction) was observed at 8 hours [2].
AMG-3969 exhibits dose-dependent effectiveness in three diabetes models: diet-induced obese (DIO), ob/ob, and db/db mice. However, it does not lower blood glucose levels in normoglycemic C57BL/6 (B6) mice. Additionally, AMG-3969 significantly enhances carbohydrate substrate utilization and induces prolonged changes in carbohydrate oxidation, evidenced by increased respiratory exchange ratio lasting into the subsequent night and day following a single dose [3].
体外研究
AMG-3969 demonstrates strong cellular activity, with an EC50 of 0.202 μM and IC50 of 4 nM [1].
It effectively counteracts GKRP's inhibition of GK activity and facilitates GK translocation in vitro (using isolated hepatocytes) [3].
作用机制
AMG-3969 may bind to a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site.[1]
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