Computer-Assisted Discovery of Retinoid X Receptor Modulating Natural Products and Isofunctional Mimetics

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.