AustralieFrV1, PubMed, Curation, bibRecord, 003529

Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.

Identifieur interne : 003529 ( PubMed/Curation ); précédent : 003528; suivant : 003530

Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.

Auteurs : Roger W. Hunter [Suisse] ; Marc Foretz [France] ; Laurent Bultot [Suisse] ; Morgan D. Fullerton [Canada] ; Maria Deak [Suisse] ; Fiona A. Ross [Royaume-Uni] ; Simon A. Hawley [Royaume-Uni] ; Natalia Shpiro [Royaume-Uni] ; Benoit Viollet [France] ; Denis Barron [Suisse] ; Bruce E. Kemp [Australie] ; Gregory R. Steinberg [Canada] ; D Grahame Hardie [Royaume-Uni] ; Kei Sakamoto [Suisse]

Source :

Chemistry & biology [ 1879-1301 ] ; 2014.

RBID : pubmed:25036776

Descripteurs français

English descriptors

KwdEn :
- AMP-Activated Protein Kinases (chemistry), AMP-Activated Protein Kinases (metabolism), Adenosine Monophosphate (pharmacology), Amino Acid Sequence, Animals, Enzyme Activation (drug effects), Enzyme Activators (metabolism), Enzyme Activators (pharmacology), Esterification (drug effects), Fatty Acids (metabolism), Hepatocytes (cytology), Hepatocytes (drug effects), Lipogenesis (drug effects), Mice, Molecular Sequence Data, Prodrugs (metabolism), Prodrugs (pharmacology), Protein Subunits (agonists), Protein Subunits (chemistry), Protein Subunits (metabolism), Recombinant Proteins (chemistry), Recombinant Proteins (metabolism), Signal Transduction (drug effects), Small Molecule Libraries (metabolism), Small Molecule Libraries (pharmacology), Substrate Specificity.
MESH :
- chemical , agonists : Protein Subunits.
- chemical , chemistry : AMP-Activated Protein Kinases, Protein Subunits, Recombinant Proteins.
- chemical , metabolism : AMP-Activated Protein Kinases, Enzyme Activators, Fatty Acids, Prodrugs, Protein Subunits, Recombinant Proteins, Small Molecule Libraries.
- chemical , pharmacology : Adenosine Monophosphate, Enzyme Activators, Prodrugs, Small Molecule Libraries.
- cytology : Hepatocytes.
- drug effects : Enzyme Activation, Esterification, Hepatocytes, Lipogenesis, Signal Transduction.
- Amino Acid Sequence, Animals, Mice, Molecular Sequence Data, Substrate Specificity.

Abstract

AMPK is a sensor of cellular energy status and a promising target for drugs aimed at metabolic disorders. We have studied the selectivity and mechanism of a recently described activator, C2, and its cell-permeable prodrug, C13. C2 was a potent allosteric activator of α1-complexes that, like AMP, also protected against Thr172 dephosphorylation. Compared with AMP, C2 caused only partial allosteric activation of α2-complexes and failed to protect them against dephosphorylation. We show that both effects could be fully restored by exchanging part of the linker between the autoinhibitory and C-terminal domains in α2, containing the equivalent region from α1 thought to interact with AMP bound in site 3 of the γ subunit. Consistent with our results in cell-free assays, C13 potently inhibited lipid synthesis in hepatocytes from wild-type and was largely ineffective in AMPK-knockout hepatocytes; its effects were more severely affected by knockout of α1 than of α2, β1, or β2.

DOI: 10.1016/j.chembiol.2014.05.014
PubMed: 25036776

Links toward previous steps (curation, corpus...)

to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :003642

Links to Exploration step

pubmed:25036776

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.</title>
<author><name sortKey="Hunter, Roger W" sort="Hunter, Roger W" uniqKey="Hunter R" first="Roger W" last="Hunter">Roger W. Hunter</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Foretz, Marc" sort="Foretz, Marc" uniqKey="Foretz M" first="Marc" last="Foretz">Marc Foretz</name>
<affiliation wicri:level="1"><nlm:affiliation>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bultot, Laurent" sort="Bultot, Laurent" uniqKey="Bultot L" first="Laurent" last="Bultot">Laurent Bultot</name>
<affiliation wicri:level="1"><nlm:affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fullerton, Morgan D" sort="Fullerton, Morgan D" uniqKey="Fullerton M" first="Morgan D" last="Fullerton">Morgan D. Fullerton</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Deak, Maria" sort="Deak, Maria" uniqKey="Deak M" first="Maria" last="Deak">Maria Deak</name>
<affiliation wicri:level="1"><nlm:affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ross, Fiona A" sort="Ross, Fiona A" uniqKey="Ross F" first="Fiona A" last="Ross">Fiona A. Ross</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hawley, Simon A" sort="Hawley, Simon A" uniqKey="Hawley S" first="Simon A" last="Hawley">Simon A. Hawley</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shpiro, Natalia" sort="Shpiro, Natalia" uniqKey="Shpiro N" first="Natalia" last="Shpiro">Natalia Shpiro</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name>
<affiliation wicri:level="1"><nlm:affiliation>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Barron, Denis" sort="Barron, Denis" uniqKey="Barron D" first="Denis" last="Barron">Denis Barron</name>
<affiliation wicri:level="1"><nlm:affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E" last="Kemp">Bruce E. Kemp</name>
<affiliation wicri:level="1"><nlm:affiliation>Protein Chemistry and Metabolism, St. Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Protein Chemistry and Metabolism, St. Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R" last="Steinberg">Gregory R. Steinberg</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hardie, D Grahame" sort="Hardie, D Grahame" uniqKey="Hardie D" first="D Grahame" last="Hardie">D Grahame Hardie</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sakamoto, Kei" sort="Sakamoto, Kei" uniqKey="Sakamoto K" first="Kei" last="Sakamoto">Kei Sakamoto</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland. Electronic address: kei.sakamoto@rd.nestle.com.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="RBID">pubmed:25036776</idno>
<idno type="pmid">25036776</idno>
<idno type="doi">10.1016/j.chembiol.2014.05.014</idno>
<idno type="wicri:Area/PubMed/Corpus">003642</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003642</idno>
<idno type="wicri:Area/PubMed/Curation">003529</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003529</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.</title>
<author><name sortKey="Hunter, Roger W" sort="Hunter, Roger W" uniqKey="Hunter R" first="Roger W" last="Hunter">Roger W. Hunter</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Foretz, Marc" sort="Foretz, Marc" uniqKey="Foretz M" first="Marc" last="Foretz">Marc Foretz</name>
<affiliation wicri:level="1"><nlm:affiliation>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bultot, Laurent" sort="Bultot, Laurent" uniqKey="Bultot L" first="Laurent" last="Bultot">Laurent Bultot</name>
<affiliation wicri:level="1"><nlm:affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fullerton, Morgan D" sort="Fullerton, Morgan D" uniqKey="Fullerton M" first="Morgan D" last="Fullerton">Morgan D. Fullerton</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Deak, Maria" sort="Deak, Maria" uniqKey="Deak M" first="Maria" last="Deak">Maria Deak</name>
<affiliation wicri:level="1"><nlm:affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ross, Fiona A" sort="Ross, Fiona A" uniqKey="Ross F" first="Fiona A" last="Ross">Fiona A. Ross</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hawley, Simon A" sort="Hawley, Simon A" uniqKey="Hawley S" first="Simon A" last="Hawley">Simon A. Hawley</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shpiro, Natalia" sort="Shpiro, Natalia" uniqKey="Shpiro N" first="Natalia" last="Shpiro">Natalia Shpiro</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name>
<affiliation wicri:level="1"><nlm:affiliation>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Barron, Denis" sort="Barron, Denis" uniqKey="Barron D" first="Denis" last="Barron">Denis Barron</name>
<affiliation wicri:level="1"><nlm:affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E" last="Kemp">Bruce E. Kemp</name>
<affiliation wicri:level="1"><nlm:affiliation>Protein Chemistry and Metabolism, St. Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Protein Chemistry and Metabolism, St. Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R" last="Steinberg">Gregory R. Steinberg</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hardie, D Grahame" sort="Hardie, D Grahame" uniqKey="Hardie D" first="D Grahame" last="Hardie">D Grahame Hardie</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sakamoto, Kei" sort="Sakamoto, Kei" uniqKey="Sakamoto K" first="Kei" last="Sakamoto">Kei Sakamoto</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland. Electronic address: kei.sakamoto@rd.nestle.com.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Chemistry & biology</title>
<idno type="eISSN">1879-1301</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (chemistry)</term>
<term>AMP-Activated Protein Kinases (metabolism)</term>
<term>Adenosine Monophosphate (pharmacology)</term>
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Enzyme Activation (drug effects)</term>
<term>Enzyme Activators (metabolism)</term>
<term>Enzyme Activators (pharmacology)</term>
<term>Esterification (drug effects)</term>
<term>Fatty Acids (metabolism)</term>
<term>Hepatocytes (cytology)</term>
<term>Hepatocytes (drug effects)</term>
<term>Lipogenesis (drug effects)</term>
<term>Mice</term>
<term>Molecular Sequence Data</term>
<term>Prodrugs (metabolism)</term>
<term>Prodrugs (pharmacology)</term>
<term>Protein Subunits (agonists)</term>
<term>Protein Subunits (chemistry)</term>
<term>Protein Subunits (metabolism)</term>
<term>Recombinant Proteins (chemistry)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>Signal Transduction (drug effects)</term>
<term>Small Molecule Libraries (metabolism)</term>
<term>Small Molecule Libraries (pharmacology)</term>
<term>Substrate Specificity</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP (pharmacologie)</term>
<term>AMP-Activated Protein Kinases ()</term>
<term>AMP-Activated Protein Kinases (métabolisme)</term>
<term>Acides gras (métabolisme)</term>
<term>Activateurs d'enzymes (métabolisme)</term>
<term>Activateurs d'enzymes (pharmacologie)</term>
<term>Activation enzymatique ()</term>
<term>Animaux</term>
<term>Bibliothèques de petites molécules (métabolisme)</term>
<term>Bibliothèques de petites molécules (pharmacologie)</term>
<term>Données de séquences moléculaires</term>
<term>Estérification ()</term>
<term>Hépatocytes ()</term>
<term>Hépatocytes (cytologie)</term>
<term>Lipogenèse ()</term>
<term>Promédicaments (métabolisme)</term>
<term>Promédicaments (pharmacologie)</term>
<term>Protéines recombinantes ()</term>
<term>Protéines recombinantes (métabolisme)</term>
<term>Souris</term>
<term>Sous-unités de protéines ()</term>
<term>Sous-unités de protéines (agonistes)</term>
<term>Sous-unités de protéines (métabolisme)</term>
<term>Spécificité du substrat</term>
<term>Séquence d'acides aminés</term>
<term>Transduction du signal ()</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Protein Subunits</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
<term>Protein Subunits</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
<term>Enzyme Activators</term>
<term>Fatty Acids</term>
<term>Prodrugs</term>
<term>Protein Subunits</term>
<term>Recombinant Proteins</term>
<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Monophosphate</term>
<term>Enzyme Activators</term>
<term>Prodrugs</term>
<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" qualifier="agonistes" xml:lang="fr"><term>Sous-unités de protéines</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Hépatocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Hepatocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Enzyme Activation</term>
<term>Esterification</term>
<term>Hepatocytes</term>
<term>Lipogenesis</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
<term>Acides gras</term>
<term>Activateurs d'enzymes</term>
<term>Bibliothèques de petites molécules</term>
<term>Promédicaments</term>
<term>Protéines recombinantes</term>
<term>Sous-unités de protéines</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>AMP</term>
<term>Activateurs d'enzymes</term>
<term>Bibliothèques de petites molécules</term>
<term>Promédicaments</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Mice</term>
<term>Molecular Sequence Data</term>
<term>Substrate Specificity</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
<term>Activation enzymatique</term>
<term>Animaux</term>
<term>Données de séquences moléculaires</term>
<term>Estérification</term>
<term>Hépatocytes</term>
<term>Lipogenèse</term>
<term>Protéines recombinantes</term>
<term>Souris</term>
<term>Sous-unités de protéines</term>
<term>Spécificité du substrat</term>
<term>Séquence d'acides aminés</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">AMPK is a sensor of cellular energy status and a promising target for drugs aimed at metabolic disorders. We have studied the selectivity and mechanism of a recently described activator, C2, and its cell-permeable prodrug, C13. C2 was a potent allosteric activator of α1-complexes that, like AMP, also protected against Thr172 dephosphorylation. Compared with AMP, C2 caused only partial allosteric activation of α2-complexes and failed to protect them against dephosphorylation. We show that both effects could be fully restored by exchanging part of the linker between the autoinhibitory and C-terminal domains in α2, containing the equivalent region from α1 thought to interact with AMP bound in site 3 of the γ subunit. Consistent with our results in cell-free assays, C13 potently inhibited lipid synthesis in hepatocytes from wild-type and was largely ineffective in AMPK-knockout hepatocytes; its effects were more severely affected by knockout of α1 than of α2, β1, or β2.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25036776</PMID>
<DateCreated><Year>2014</Year>
<Month>07</Month>
<Day>19</Day>
</DateCreated>
<DateCompleted><Year>2015</Year>
<Month>08</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>11</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1879-1301</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>21</Volume>
<Issue>7</Issue>
<PubDate><Year>2014</Year>
<Month>Jul</Month>
<Day>17</Day>
</PubDate>
</JournalIssue>
<Title>Chemistry & biology</Title>
<ISOAbbreviation>Chem. Biol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.</ArticleTitle>
<Pagination><MedlinePgn>866-79</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.chembiol.2014.05.014</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">S1074-5521(14)00202-6</ELocationID>
<Abstract><AbstractText>AMPK is a sensor of cellular energy status and a promising target for drugs aimed at metabolic disorders. We have studied the selectivity and mechanism of a recently described activator, C2, and its cell-permeable prodrug, C13. C2 was a potent allosteric activator of α1-complexes that, like AMP, also protected against Thr172 dephosphorylation. Compared with AMP, C2 caused only partial allosteric activation of α2-complexes and failed to protect them against dephosphorylation. We show that both effects could be fully restored by exchanging part of the linker between the autoinhibitory and C-terminal domains in α2, containing the equivalent region from α1 thought to interact with AMP bound in site 3 of the γ subunit. Consistent with our results in cell-free assays, C13 potently inhibited lipid synthesis in hepatocytes from wild-type and was largely ineffective in AMPK-knockout hepatocytes; its effects were more severely affected by knockout of α1 than of α2, β1, or β2.</AbstractText>
<CopyrightInformation>Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hunter</LastName>
<ForeName>Roger W</ForeName>
<Initials>RW</Initials>
<AffiliationInfo><Affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Foretz</LastName>
<ForeName>Marc</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bultot</LastName>
<ForeName>Laurent</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fullerton</LastName>
<ForeName>Morgan D</ForeName>
<Initials>MD</Initials>
<AffiliationInfo><Affiliation>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Deak</LastName>
<ForeName>Maria</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ross</LastName>
<ForeName>Fiona A</ForeName>
<Initials>FA</Initials>
<AffiliationInfo><Affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hawley</LastName>
<ForeName>Simon A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Shpiro</LastName>
<ForeName>Natalia</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Viollet</LastName>
<ForeName>Benoit</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Barron</LastName>
<ForeName>Denis</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kemp</LastName>
<ForeName>Bruce E</ForeName>
<Initials>BE</Initials>
<AffiliationInfo><Affiliation>Protein Chemistry and Metabolism, St. Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Steinberg</LastName>
<ForeName>Gregory R</ForeName>
<Initials>GR</Initials>
<AffiliationInfo><Affiliation>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hardie</LastName>
<ForeName>D Grahame</ForeName>
<Initials>DG</Initials>
<AffiliationInfo><Affiliation>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sakamoto</LastName>
<ForeName>Kei</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland. Electronic address: kei.sakamoto@rd.nestle.com.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>097726</GrantID>
<Agency>Wellcome Trust</Agency>
<Country>United Kingdom</Country>
</Grant>
<Grant><Agency>Canadian Institutes of Health Research</Agency>
<Country>Canada</Country>
</Grant>
<Grant><Agency>Medical Research Council</Agency>
<Country>United Kingdom</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Chem Biol</MedlineTA>
<NlmUniqueID>9500160</NlmUniqueID>
<ISSNLinking>1074-5521</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D020536">Enzyme Activators</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D005227">Fatty Acids</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011355">Prodrugs</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D021122">Protein Subunits</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054852">Small Molecule Libraries</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>415SHH325A</RegistryNumber>
<NameOfSubstance UI="D000249">Adenosine Monophosphate</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D055372">AMP-Activated Protein Kinases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Toxicol Appl Pharmacol. 2013 Dec 1;273(2):325-34</RefSource>
<PMID Version="1">24055643</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2011 Apr 14;472(7342):230-3</RefSource>
<PMID Version="1">21399626</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell Metab. 2013 Oct 1;18(4):556-66</RefSource>
<PMID Version="1">24093679</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Struct Mol Biol. 2012 Jul;19(7):716-8</RefSource>
<PMID Version="1">22659875</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biosci Biotechnol Biochem. 2010;74(3):548-52</RefSource>
<PMID Version="1">20208361</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2010 Nov 26;285(48):37198-209</RefSource>
<PMID Version="1">20855892</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Regul Integr Comp Physiol. 2003 Apr;284(4):R936-44</RefSource>
<PMID Version="1">12626360</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Annu Rev Biochem. 2006;75:137-63</RefSource>
<PMID Version="1">16756488</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Anal Biochem. 1988 Jun;171(2):266-70</RefSource>
<PMID Version="1">3044186</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Clin Invest. 2003 Jan;111(1):91-8</RefSource>
<PMID Version="1">12511592</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Curr Biol. 2003 May 13;13(10):861-6</RefSource>
<PMID Version="1">12747836</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Diabetes. 1991 Oct;40(10):1259-66</RefSource>
<PMID Version="1">1657665</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Physiol Rev. 2009 Jul;89(3):1025-78</RefSource>
<PMID Version="1">19584320</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Science. 2011 Jun 17;332(6036):1433-5</RefSource>
<PMID Version="1">21680840</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biochem Biophys Res Commun. 2014 Jan 10;443(2):435-40</RefSource>
<PMID Version="1">24332941</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2007 Sep 27;449(7161):496-500</RefSource>
<PMID Version="1">17851531</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2010 Jan 1;285(1):115-22</RefSource>
<PMID Version="1">19892703</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2004 Jan 9;279(2):1070-9</RefSource>
<PMID Version="1">14573616</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Diabetes. 2011 Mar;60(3):766-74</RefSource>
<PMID Version="1">21282366</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Chem Biol. 2012 Oct 26;19(10):1222-36</RefSource>
<PMID Version="1">23102217</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell Metab. 2006 Jun;3(6):403-16</RefSource>
<PMID Version="1">16753576</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biochem J. 1999 Mar 15;338 ( Pt 3):783-91</RefSource>
<PMID Version="1">10051453</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Clin Invest. 2010 Jul;120(7):2355-69</RefSource>
<PMID Version="1">20577053</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2013 Jun 13;498(7453):E8-10</RefSource>
<PMID Version="1">23765502</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Life Sci. 1988;43(5):437-44</RefSource>
<PMID Version="1">2899829</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>ACS Med Chem Lett. 2010 Aug 30;1(9):478-82</RefSource>
<PMID Version="1">24900234</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Science. 2012 May 18;336(6083):918-22</RefSource>
<PMID Version="1">22517326</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Heart Circ Physiol. 2014 Jun 15;306(12):H1619-30</RefSource>
<PMID Version="1">24748590</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>IUBMB Life. 2009 Jan;61(1):18-26</RefSource>
<PMID Version="1">18798311</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Can J Biochem Physiol. 1959 Aug;37(8):911-7</RefSource>
<PMID Version="1">13671378</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E665-75</RefSource>
<PMID Version="1">19531644</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Med. 2013 Dec;19(12):1649-54</RefSource>
<PMID Version="1">24185692</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Commun. 2013;4:3017</RefSource>
<PMID Version="1">24352254</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2007 Nov 9;282(45):32539-48</RefSource>
<PMID Version="1">17728241</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>FEBS Lett. 1996 Nov 18;397(2-3):347-51</RefSource>
<PMID Version="1">8955377</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2007 Nov 9;282(45):32549-60</RefSource>
<PMID Version="1">17855357</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16092-7</RefSource>
<PMID Version="1">21896769</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Chem Biol. 2008 Nov 24;15(11):1220-30</RefSource>
<PMID Version="1">19022182</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biochem J. 1998 Aug 15;334 ( Pt 1):177-87</RefSource>
<PMID Version="1">9693118</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E310-7</RefSource>
<PMID Version="1">15068958</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell Res. 2013 Oct;23(10):1237-40</RefSource>
<PMID Version="1">23999859</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2008 Jun 6;283(23):16051-60</RefSource>
<PMID Version="1">18321858</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Chem Biol. 2014 May 22;21(5):619-27</RefSource>
<PMID Version="1">24746562</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E29-37</RefSource>
<PMID Version="1">18477703</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Endocrinol Metab. 2014 Mar;306(6):E688-96</RefSource>
<PMID Version="1">24425763</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1996 Nov 1;271(44):27879-87</RefSource>
<PMID Version="1">8910387</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Am J Physiol. 1997 Dec;273(6 Pt 1):E1107-12</RefSource>
<PMID Version="1">9435525</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
<MeshHeadingList><MeshHeading><DescriptorName UI="D055372" MajorTopicYN="N">AMP-Activated Protein Kinases</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004789" MajorTopicYN="N">Enzyme Activation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020536" MajorTopicYN="N">Enzyme Activators</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004951" MajorTopicYN="N">Esterification</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005227" MajorTopicYN="N">Fatty Acids</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D022781" MajorTopicYN="N">Hepatocytes</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050155" MajorTopicYN="N">Lipogenesis</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011355" MajorTopicYN="N">Prodrugs</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D021122" MajorTopicYN="N">Protein Subunits</DescriptorName>
<QualifierName UI="Q000819" MajorTopicYN="N">agonists</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054852" MajorTopicYN="N">Small Molecule Libraries</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013379" MajorTopicYN="N">Substrate Specificity</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<OtherID Source="NLM">PMC4104029</OtherID>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year>
<Month>02</Month>
<Day>17</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2014</Year>
<Month>05</Month>
<Day>09</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2014</Year>
<Month>05</Month>
<Day>30</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2014</Year>
<Month>7</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2014</Year>
<Month>7</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2015</Year>
<Month>8</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">25036776</ArticleId>
<ArticleId IdType="pii">S1074-5521(14)00202-6</ArticleId>
<ArticleId IdType="doi">10.1016/j.chembiol.2014.05.014</ArticleId>
<ArticleId IdType="pmc">PMC4104029</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/PubMed/Curation

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003529 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd -nk 003529 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    PubMed
   |étape=   Curation
   |type=    RBID
   |clé=     pubmed:25036776
   |texte=   Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i   -Sk "pubmed:25036776" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Dec 5 10:43:12 2017. Site generation: Tue Mar 5 14:07:20 2024

	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur les relations entre la France et l'Australie

Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.

Mechanism of action of compound-13: an α1-selective small molecule activator of AMPK.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki