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在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
ZLN024 hydrochloride is an AMPK allosteric activator. ZLN024 directly activates recombinant AMPK α1β1γ1 , AMPK α2β1γ1 , AMPK α1β2γ1 and AMPK α2β2γ1 heterotrimer with EC 50 s of 0.42 µM, 0.95 µM, 1.1 µM and 0.13 µM, respectively.
In Vitro
ZLN024 allosterically stimulates active AMPK heterotrimers and the inactive α1 subunit truncations α1 (1-394) and α1 (1-335) but not α1 (1-312). AMPK activation by ZLN024 requires the pre-phosphorylation of Thr-172 by at least one upstream kinase and protects AMPK Thr-172 against dephosphorylation by PP2Cα. ZLN024 activates AMPK in L6 myotubes and stimulates glucose uptake and fatty acid oxidation without increasing the ADP/ATP ratio. Using the established scintillation proximity assay (SPA) assay, random screening against the AMPK α1β1γ1 heterotrimer is performed and a new AMPK activator, ZLN024 is found. ZLN024 directly activates recombinant AMPK α1β1γ1 and its homologue α2β1γ1 in a concentration-dependent manner. ZLN024 increases the activity of α1β1γ1 by 1.5-fold and has an EC 50 of 0.42 µM, and it increases the activity of α2β1γ1 by 1.7-fold with an EC 50 of 0.95 µM. ZLN024 also directly activates recombinant AMPK α1β2γ1, by 1.7-fold with an EC 50 of 1.1 µM; and AMPK α2β2γ1, by 1.6-fold with an EC 50 of 0.13 µM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
C57BKS db/db mice are administered a 15 mg/kg/day dose of ZLN024 by daily gavage for 5 weeks; 250 mg/kg/day Metformin (Met) is used as a positive control. During the treatment period, there is no significant alteration in food intake and body weight compared with the vehicle group. After 4 weeks of treatment, ZLN024 improves glucose tolerance. ZLN024 reduces the fasting blood glucose by 15%. Liver tissue weight, triacylglycerol and the total cholesterol content are decreased . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:AMPK α2β2γ1 0.13 μM (EC 50 ) AMPK α1β1γ1 0.42 μM (EC 50 ) AMPK α2β1γ1 0.95 μM (EC 50 )
分类树(Taxonomy Tree)
| 界(kingdom) | 有机化合物 |
|---|---|
| 超类(Superclass) | 苯类化合物 |
| 类(Class) | 酚醚 |
| 亚类(Subclass) | 暂无 |
| 中间层级节点(Intermediate Tree Nodes) | 暂无 |
| 直接上位类(Direct Parent) | 酚醚 |
| 其他上位类(Alternative Parents) | 苯氧基化合物 甲苯 溴苯类 烷基芳基硫醚 烷基芳基醚 嘧啶和嘧啶衍生物 芳基溴化物 杂芳族化合物 亚磺酰基化合物 氮杂环化合物 有机氮化合物 有机溴化物 盐酸盐 碳氢化合物衍生物 |
| 分子骨架(Molecular Framework) | 芳香族杂单环化合物 |
| 取代基(Substituents) | 芳基醚 - 烷基芳硫醚 - 芳香族杂单环化合物 - 芳基溴化物 - 芳基卤化物 - 芳基硫醚 - 氮杂环 - 溴苯 - 乙醚 - 卤苯 - 杂芳香族化合物 - 烃衍生物 - 氟氯烃 - 单环苯基基团 - 有机硝基化合物 - 有机氧化合物 - 有机硒化合物 - 有机卤化物 - 有机杂环化合物 - 有机氮化合物 - 有机氧化合物 - 有机硫化合物 - 苯酚醚 - 苯氧基化合物 - 嘧啶 - 硫酰基化合物 - 硫醚 - 甲苯 |
| 描述(Description) | 该化合物属于酚醚类有机化合物。这类芳香化合物含有以苯环取代的醚基团。 |
| 外部描述符(External Descriptors) | 暂无 |