ZLN 024 hydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ZLN 024 Hydrochloride 是一种 AMPK 变构激活剂，可刺激非活性 α1 亚基截短 α1 (1-394) 和 α1 (1-335)，但不刺激 α1 (1-312)。

ZLN 024 hydrochloride is an AMPK allosteric activator and stimulates the inactive α1 subunit truncations α1 (1-394) and α1 (1-335) but not α1 (1-312).(In Vitro):ZLN 024 hydrochloride increases the activity of α1β1γ1 by 1.5-fold and has an EC50 of 0.42 μM, and it increases the activity of α2β1γ1 by 1.7-fold with an EC50 of 0.95 μM. ZLN 024 hydrochloride also directly activates recombinant AMPK α1β2γ1, by 1.7-fold with an EC50 of 1.1 μM; and AMPK α2β2γ1, by 1.6-fold with an EC50 of 0.13 μM. ZLN 024 hydrochloride directly activates recombinant AMPK α1β1γ1 and its homolog α2β1γ1 in a concentration-dependent manner.(In Vivo):In C57BKS db/db mice, ZLN 024 hydrochloride(15 mg/kg/day; oral) improves glucose tolerance after 4 weeks of treatment. ZLN 024 hydrochloride reduces the fasting blood glucose by 15%. Liver tissue weight, triacylglycerol and the total cholesterol content are decreased.

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

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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Membrane Transporter/Ion Channel

AMPK

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1883548-91-1

361.68

C13H14BrClN2OS

>98% (HPLC)

In Vitro:?DMSO : ≥ 46 mg/mL (127.18 mM)

BrC1=C(C=CC(C)=C1)OCCSC2=NC=CC=N2.Cl

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(-20℃)

With Ice Pack

≥ 2 years