Abstract: The present invention features inhibitors of the eIF4A enzyme. These inhibitors have a novel mechanism for inhibiting the eIF4A enzyme by occupying a binding pocket within the eIF4A RNA-binding groove, thereby perturbing RNA binding, blocking ATP hydrolysis, and, consequently, inhibiting RNA helicase activity. Thus, the compounds of the present invention are RNA-competitive, ATP-uncompetitive elF4A inhibitors that directly bind elF4A and inhibit the protein.