AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern

D Grahame Hardie; Fiona A Ross; Simon A Hawley

doi:10.1016/j.chembiol.2012.08.019

AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern

D Grahame Hardie (Lead / Corresponding author), Fiona A Ross, Simon A Hawley

Research output: Contribution to journal › Review article › peer-review

315 Citations (Scopus)

216 Downloads (Pure)

Abstract

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.

Original language	English
Pages (from-to)	1222-36
Number of pages	15
Journal	Chemistry & Biology
Volume	19
Issue number	10
DOIs	https://doi.org/10.1016/j.chembiol.2012.08.019
Publication status	Published - 26 Oct 2012

Keywords

AMP-Activated Protein Kinases
Anti-Bacterial Agents
Diabetes Mellitus, Type 2
Humans
Hypoglycemic Agents
Metformin
Neoplasms
Protein-Serine-Threonine Kinases
Salicylates
Journal Article
Research Support, Non-U.S. Gov't
Review

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chembiol.2012.08.019

Author accepted manuscript
© 2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 1.5 MBLicence: CC BY-NC-ND

Non-canonical Pathways for Regulation of AMPK (Senior Investigator Award)
Hardie, G. (Investigator)
1/04/12 → 30/09/17
Project: Research

Cite this

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title = "AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern",

abstract = "The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.",

keywords = "AMP-Activated Protein Kinases, Anti-Bacterial Agents, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Neoplasms, Protein-Serine-Threonine Kinases, Salicylates, Journal Article, Research Support, Non-U.S. Gov't, Review",

author = "Hardie, {D Grahame} and Ross, {Fiona A} and Hawley, {Simon A}",

note = "Studies in the authors{\textquoteright} laboratory have been supported by the Wellcome Trust, Cancer Research UK, and the companies AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Merck Serono, and Pfizer, which support the Division of Signal Transduction Therapy at the University of Dundee.",

year = "2012",

month = oct,

day = "26",

doi = "10.1016/j.chembiol.2012.08.019",

language = "English",

volume = "19",

pages = "1222--36",

journal = "Chemistry & Biology",

issn = "1074-5521",

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number = "10",

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T1 - AMP-Activated Protein Kinase

T2 - A Target for Drugs both Ancient and Modern

AU - Hardie, D Grahame

AU - Ross, Fiona A

AU - Hawley, Simon A

N1 - Studies in the authors’ laboratory have been supported by the Wellcome Trust, Cancer Research UK, and the companies AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Merck Serono, and Pfizer, which support the Division of Signal Transduction Therapy at the University of Dundee.

PY - 2012/10/26

Y1 - 2012/10/26

N2 - The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.

AB - The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.

KW - AMP-Activated Protein Kinases

KW - Anti-Bacterial Agents

KW - Diabetes Mellitus, Type 2

KW - Humans

KW - Hypoglycemic Agents

KW - Metformin

KW - Neoplasms

KW - Protein-Serine-Threonine Kinases

KW - Salicylates

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Review

U2 - 10.1016/j.chembiol.2012.08.019

DO - 10.1016/j.chembiol.2012.08.019

M3 - Review article

C2 - 23102217

SN - 1074-5521

VL - 19

SP - 1222

EP - 1236

JO - Chemistry & Biology

JF - Chemistry & Biology

IS - 10

ER -

AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern

Abstract

Keywords

UN SDGs

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Projects

Non-canonical Pathways for Regulation of AMPK (Senior Investigator Award)

Cite this