Discovery of Novel Myc—Max Heterodimer Disruptors with a Three-Dimensional Pharmacophore Model

摘要

A three-dimensional pharmacophore model was generated utilizing a set of known inhibitors of c-Myc---Max heterodimer formation. The model successfully identified a set of structurally diverse compounds with potential inhibitory activity against c-Myc. Nine compounds were tested in vitro, and four displayed affinities in the micromolar range and growth inhibitory activity against c-Mycoverexpressing cells. These studies demonstrate the applicability of pharmacophore modeling to the identification of novel and potentially more puissant inhibitors of the c-Myc oncoprotein.