title: Past strategies and future directions for identifying AMP-activated protein kinase (AMPK) modulators.
abstract: AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs.
authors.affiliation: Neurobiology Curriculum, University of North Carolina at Chapel Hill (UNC), United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Sinnett
authors.affiliation: UNC Neuroscience Center, United States; Department of Cell Biology and Physiology, UNC, United States. Electronic address: brenman@med.unc.edu.
authors.forename: Jay E
authors.initials: JE
authors.lastname: Brenman
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D000818:Animals; D055808:Drug Discovery; D020035:Holoenzymes / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D020035:Holoenzymes; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Dephosphorylation inhibition; Drug discovery; High-throughput screening; Nucleotide analogs; Regulatory fragment