Identification of Non-Peptide Malignant Brain Tumor (MBT) Repeat Antagonists by Virtual Screening of Commercially Available Compounds
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- 作者：Dmitri Kireev ; Tim J. Wigle ; Jacqueline Norris-Drouin ; J. Martin Herold ; William P. Janzen ; Stephen V. Frye
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：November 11, 2010
- 年：2010
- 卷：53
- 期：21
- 页码：7625-7631
- 全文大小：861K
- 年卷期：v.53,no.21(November 11, 2010)
- ISSN：1520-4804
文摘
The malignant brain tumor (MBT) repeat is an important epigenetic-code “reader” and is functionally associated with differentiation, gene silencing, and tumor suppression.(1-3) 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.