title: BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase.
abstract: BMS309403 is a biphenyl azole inhibitor against fatty acid binding protein 4 (FABP4) and regarded as a lead compound for effective treatment of obesity related cardio-metabolic diseases. Here we discovered an off-target activity of BMS309403 in that it stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent manner via activation of AMP-activated protein kinase (AMPK) signaling pathway but independent of FABPs. Further analysis indicated that BMS309403 activates AMPK through increasing the ratio of intracellular AMP:ATP while decreasing mitochondrial membrane potential. These findings provide mechanistic insights on the action of BMS309403.
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Lin
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Huang
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.forename: Dongye
authors.initials: D
authors.lastname: Wang
authors.forename: Qilong
authors.initials: Q
authors.lastname: Peng
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Jingya
authors.initials: J
authors.lastname: Li
authors.forename: Xiujie
authors.initials: X
authors.lastname: Liu
authors.forename: Kuai
authors.initials: K
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C559288:2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid; D001713:Biphenyl Compounds; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D011720:Pyrazoles; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose