Computer-Assisted Discovery of Retinoid X Receptor Modulating Natural Products and Isofunctional Mimetics
Daniel J. Merk, Francesca Grisoni, Lukas Friedrich, Elena Gelžinytė, Gisbert Schneider · Journal of Medicinal Chemistry · 2018
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.