Beyond AICA riboside: In search of new specific AMP‐activated protein kinase activators
Open accessAbstract
5‐Aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICA riboside) has been extensively used in vitro and in vivo to activate the AMP‐activated protein kinase (AMPK), a metabolic sensor involved in both cellular and whole body energy homeostasis. However, it has been recently highlighted that AICA riboside also exerts AMPK‐independent effects, mainly on AMP‐regulated enzymes and mitochondrial oxidative phosphorylation (OXPHOS), leading to the conclusion that new compounds with reduced off target effects are needed to specifically activate AMPK. Here, we review recent findings on newly discovered AMPK activators, notably on A‐769662, a nonnucleoside compound from the thienopyridone family. We also report that A‐769662 is able to activate AMPK and stimulate glucose uptake in both L6 cells and primary myotubes derived from human satellite cells. In addition, A‐769662 increases AMPK activity and phosphorylation of its main downstream targets in primary cultured rat hepatocytes but, by contrast with AICA riboside, does neither affect mitochondrial OXPHOS nor change cellular AMP:ATP ratio. We conclude that A‐769662 could be one of the new promising chemical agents to activate AMPK with limited AMPK‐independent side effects. © 2008 IUBMB IUBMB Life, 61(1): 18–26, 2009
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A769662, a non-nucleoside compound thienopyridone, activates AMPK to stimulate glucose uptake in vitro.
“New promising candidates include A769662, a non-nucleoside compound thienopyridone that activates AMPK to stimulate glucose uptake in vitro 163.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [163]
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- Authors
- Guigas, B., Sakamoto, K., Taleux, N., Reyna, S. M., Musi, N., Viollet, B., & Hue, L.
- Affiliations
- Leiden University Medical Center (NL)
- University of Dundee (GB)
- Inserm (FR)
- Texas Diabetes Institute (US)
- de Duve Institute (BE)
- Corresponding author
- Guigas, Bruno
- Venue
- IUBMB Life
- Publisher
- Wiley
- Published
- 2008-09-16
- Volume
- 61
- Issue
- 1
- Pages
- 18-26
- ISSN
- 1521-6543 (ISSN-L)
- 1521-6551
- PMC
- PMC2845387
- OpenAlex
- W1993655397
- Cited by
- 86
- References
- 52
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2022: 2 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 4
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- IUBMB Life (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Merck KGaA
- Diabetes UK (07/0003529)
- European Commission (LSHMCT-2004-005272)
- Fonds De La Recherche Scientifique - FNRS
- National Institutes of Health (07/0003529)
- Medical Research Council (07/0003529)
- National Institute on Aging (AG-030979, K23AG030979)
- National Heart, Lung, and Blood Institute (HL086089, F32HL086089)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080157, DK-080157)
- National Institute on Minority Health and Health Disparities (L60 MD000986)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- AMPK, AMPK activators, AICA riboside, A769662, mitochondrial oxidative phosphorylation, AMP/ATP ratio, glucose uptake, myotubes, hepatocytes, energy homeostasis, nucleoside analogues
- MeSH terms
- Aminoimidazole Carboxamide, Biphenyl Compounds, Glucose, Homeostasis, Humans, Phosphorylation, Pyrones, Ribonucleosides, Thiophenes, Molecular Structure, Enzyme Activators, AMP-Activated Protein Kinases
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