Virtual Screening for Dual Hsp90/B-Raf Inhibitors

  • Andrew Anighoro
  • Luca Pinzi
  • Giulio Rastelli
  • Jürgen BajorathEmail author
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


In this chapter, we describe a computational strategy leading to the identification of the first dual inhibitors of Heat Shock Protein 90 (Hsp90) and protein kinase B-Raf. Both proteins are validated targets for anti-cancer drug discovery. There is strong evidence that the simultaneous inhibition of Hsp90 and B-Raf provides therapeutic benefits compared to exclusive engagement of one or the other target. Hence, we have been interested in searching for dual Hsp90/B-Raf inhibitors. Virtual compound screening led to the identification of two compounds with micromolar activity against both targets. The computational approach faced a number of challenges that needed to be overcome, as described herein.


B-Raf Hsp90 Molecular docking Multi-target inhibitors Pharmacophores Polypharmacology Virtual screening 



We thank OpenEye Scientific Software, Inc., for a free academic license of the OpenEye Toolkit and Chemical Computing Group, Inc., for academic teaching licences of the Molecular Operating Environment.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Andrew Anighoro
    • 1
  • Luca Pinzi
    • 2
  • Giulio Rastelli
    • 2
  • Jürgen Bajorath
    • 1
    Email author
  1. 1.Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal ChemistryRheinische Friedrich-Wilhelms-UniversitätBonnGermany
  2. 2.Department of Life SciencesUniversity of Modena and Reggio EmiliaModenaItaly

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