HSP90 Ligands Chemical Diversity of Known Molecules and Discovery of New Potential Hits by Virtual Screening

presentation · 14 years ago
by Davide Audisio (Aureus Pharma)
Screen JKlustor Calculator Plugins (logP logD pKa etc...)

Hsp90 has emerged as a promising target for new cancer therapeutics, with the perspective of simultaneous disruption of a large range of oncogenic pathways. HSP 90 Inhibitors could result in cytostasis or cell death. Diverse inhibitors of this chaperone protein are currently under intensive study due to their potential role in regulating cellular proliferation.

Patented and published structure-activity relationships on HSP90 inhibitors were organized in the Aureus Pharma knowledgedatabase format. The HSP90 dataset contains chemical structures linked to their biological activities as well as the detailed description of the experimental protocols used for biological testing. Chemical diversity analysis were performed using either the molecular descriptors calculated with Calculator Plugins (ChemAxon) and a radar-type visualization or by clustering using JKlustor (ChemAxon). Active molecules were extracted and diverse representative derivatives were selected as query molecules to screen the Zinc database. This virtual screening was performed using ChemAxon pharmacophoric fingerprints to identify new HSP90 inhibitors. Several hits were identified at different similarity thresholds and selected on the basis of their chemical novelty for biological testing. Experimental validation is in progress.