Department of Chemistry and Applied Biosciences , Swiss Federal Institute of Technology (ETH) , Vladimir-Prelog-Weg 4 , CH-8093 Zurich , Switzerland.
Department of Earth and Environmental Sciences , University of Milano-Bicocca , Piazza della Scienza, 1 , IT-20126 Milan , Italy.
J Med Chem. 2018 Jun 28;61(12):5442-5447. doi: 10.1021/acs.jmedchem.8b00494. Epub 2018 Jun 14.
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.
天然产物 (NPs) 逐渐被认为是药理学工具和先导结构的宝贵来源。为了实现基于 NP 的视黄醇 X 受体 (RXR) 调节剂设计，通过计算方法鉴定了三种新型靶向 RXR 的 NPs。其中，缬草酸被发现对 RXRβ 具有选择性，使其成为独特的药理学工具化合物。然后，这些 NPs 作为模板，通过自动化、基于配体的从头设计，创新性地设计出易于获得的类似物，这些类似物继承了天然模板的生物学活性。
