molecules of the month

compound 14d

β2-AMPK activator

in vivo efficacy in diabetic mouse model

scaffold hopping from MK-8722 + opt.

Bioorg. Med. Chem. Lett., 17 November 2022

Shionogi & Co., Osaka, JP

compound 14d chemical structure β2-AMPK activator- Shionogi & Co., Osaka, JP
4 mins read

Revisiting AMPK activation with β2-AMPK isoform potency. “Compound 14d” (Shionogi & Co.) is a highly potent, dose-dependent adenosine monophosphate activated protein kinase (AMPK) activator being investigated for its blood-glucose-lowering effects. AMPK became a target-of-interest for the treatment of diabetes due to its role in regulating of glucose and lipid metabolism. Activation of AMPK switches on catabolic pathways, generates ATP, and ultimately inhibits glucogenesis. Indirect AMPK activators increase the AMP-ATP ratio, causing a conformational change and activation upon AMP binding to γ-subunits. AMPK is indirectly activated by one of the most widely prescribed drugs for Type 2 diabetes mellitus, metformin (Glucophage), with more than 92 million prescriptions filled in the US in 2020, making it the third most-commonly prescribed medication. The…

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