Identification of Non-Peptide Malignant Brain Tumor (MBT) Repeat Antagonists by Virtual Screening of Commercially Available Compounds

The malignant brain tumor (MBT) repeat is an important epigenetic-code “reader” and is functionally associated with differentiation, gene silencing, and tumor suppression.− Small molecule probes of MBT domains should enable a systematic study of MBT-containing proteins and potentially reveal novel druggable targets. We designed and applied a virtual screening strategy that identified potential MBT antagonists in a large database of commercially available compounds. A small set of virtual hits was purchased and submitted to experimental testing. Nineteen of the purchased compounds showed a specific dose-dependent protein binding and will provide critical structure−activity information for subsequent lead generation and optimization.