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.
CITATION STYLE
Anighoro, A., Pinzi, L., Rastelli, G., & Bajorath, J. (2019). Virtual screening for dual Hsp90/B-Raf inhibitors. In Methods in Pharmacology and Toxicology (pp. 355–365). Humana Press Inc. https://doi.org/10.1007/7653_2017_1
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