Discovery of small molecule activators of the Slack potassium channel for use as cell-based probes for the study of fragile X syndrome

PROJECT NARRATIVE Fragile X syndrome (FXS) is a genetic disorder that is the most common inherited cause of intellectual disability and often comorbid with autism spectrum disorder (ASD). Epigenetic silencing of the FMR1 gene in FXS results in a deficiency of the Fragile X mental retardation protein (FMRP), a binding protein that activates Slack potassium channels. Drugs that activate Slack channels may provide effective treatments for FXS, and potent and selective Slack activator cell-based probes are required to validate this therapeutic approach.