ZLN024 is an activator of AMPK allosteric. 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 α2β1γ1:0.95 μM (EC50), AMPK α1β2γ1:1.1 µM, AMPK α1β1γ1:0.42 μM (EC50), AMPK α2β2γ1:0.13 μM (EC50)

ZLN024 allosterically stimulates active AMPK heterotrimers and the inactive α1 subunit truncations α1 (1-394) and α1 (1-335) but not α1 (1-312). It increases the activity of α1β1γ1 by 1.5-fold with an EC50 of 0.42 μM, α2β1γ1 by 1.7-fold with an EC50 of 0.95 μM, 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. After 4 weeks of treatment, ZLN024 improves glucose tolerance, reduces fasting blood glucose by 15%, and decreases liver tissue weight, triacylglycerol, and total cholesterol content.