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ZLN024 hydrochloride

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产品价格:电议      采购度:1591      原产地:美洲

发布时间:2021/7/29 18:38:10      所属地区:上海 上海市

简要描述:

ZLN024 hydrochloride 是一种 AMPK 变构激活剂。ZLN024 直接激活重组 AMPK α1β1γ1,AMPK α2β1γ1,AMPK α1β2γ1 和 AMPK α2β2γ1 异源三聚体,EC50 分别为 μM, μM, μM 和 μM。

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ZLN024 hydrochloride

CAS No. : 1883548-91-1

MCE 站:ZLN024 hydrochloride

产品活性:ZLN024 hydrochloride 是一种 AMPK 变构激活剂。ZLN024 直接激活重组 AMPK α1β1γ1,AMPK α2β1γ1,AMPK α1β2γ1 和 AMPK α2β2γ1 异源三聚体,EC50 分别为 0.42 μM,0.95 μM,1.1 μM 和 0.13 μM。

研究领域:Epigenetics  |  PI3K/Akt/mTOR

作用靶点:AMPK

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 EC50 of 0.42 ?M, and it increases the activity of α2β1γ1 by 1.7-fold with an EC50 of 0.95 ?M. ZLN024 also directly activates recombinant AMPK α1β2γ1, by 1.7-fold with an EC50 of 1.1 ?M; and AMPK α2β2γ1, by 1.6-fold with an EC50 of 0.13 ?M.

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.

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更新时间:2024/1/2 10:17:03

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