The ancient drug salicylate directly activates AMP-activated protein kinase.

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Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG

The ancient drug salicylate directly activates AMP-activated protein kinase.

Science. 2012 May 18;336(6083):918-22. doi: 10.1126/science.1215327. Epub 2012 Apr 19.

PubMed ID

22517326 [ View in PubMed

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Abstract

Salicylate, a plant product, has been in medicinal use since ancient times. More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates adenosine monophosphate-activated protein kinase (AMPK), a central regulator of cell growth and metabolism. Salicylate binds at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site, threonine-172. In AMPK knockout mice, effects of salicylate to increase fat utilization and to lower plasma fatty acids in vivo were lost. Our results suggest that AMPK activation could explain some beneficial effects of salsalate and aspirin in humans.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	5'-AMP-activated protein kinase (Protein Group)	Protein group	Humans	Unknown	Activator	Details

Polypeptides

Name	UniProt ID
5'-AMP-activated protein kinase catalytic subunit alpha-2	P54646	Details