A High Throughput Assay for Discovery of Small Molecules that Bind AMP-activated Protein Kinase (AMPK).

ABSTRACT: AMPK is a conserved heterotrimeric serine-threonine kinase that regulates anabolic and catabolic pathways in eukaryotes. Its central role in cellular and whole body metabolism makes AMPK a commonly proposed therapeutic target for illnesses characterized by abnormal energy regulation, including cancer and diabetes. Many AMPK modulators, however, produce AMPK-independent effects. To identify drugs that modulate AMPK activity independent of the canonical ATP-binding pocket found throughout the kinome, we designed a robust fluorescence-based high throughput screening assay biased toward the identification of molecules that bind the regulatory region of AMPK through displacement of MANT-ADP, a fluorescent ADP analog. Automated pin tools were used to rapidly transfer small molecules to a low vol

SUBMITTER: Sinnett SE 

PROVIDER: S-EPMC3854666 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature