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Published on: August 16, 2018
Computer-Assisted Discovery of Retinoid X Receptor Modulating Natural Products and Isofunctional Mimetics
Daniel Merk1, Francesca Grisoni1,2, Lukas Friedrich1
1Department of Chemistry and Applied Biosciences , Swiss Federal Institute of Technology (ETH) , Vladimir-Prelog-Weg 4 , CH-8093 Zurich , Switzerland.
Abstract:
Natural products (NPs) are progressively recognized as invaluable source of pharmacological tools and lead structures. To enable NP-inspired retinoid X receptor (RXR) modulator design, three novel RXR-targeting NPs were computationally identified. Among them, valerenic acid was found to be selective for RXRβ, rendering it a unique pharmacological tool compound. The NPs then served as templates for automated, ligand-based de novo design of innovative, easily accessible mimetics that inherited the biological activities of their natural templates.
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