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

J Med Chem. 2018 Jun 28;61(12):5442-5447. doi: 10.1021/acs.jmedchem.8b00494. Epub 2018 Jun 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemistry
  • Abietanes / pharmacology
  • Biological Products / chemistry*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Computational Biology / methods*
  • Drug Discovery / methods
  • Drug Evaluation, Preclinical / methods
  • Hep G2 Cells
  • Humans
  • Indenes / chemistry
  • Indenes / pharmacology*
  • Ligands
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology
  • Retinoid X Receptors / agonists
  • Retinoid X Receptors / chemistry
  • Retinoid X Receptors / metabolism*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*

Substances

  • Abietanes
  • Biological Products
  • Carboxylic Acids
  • Indenes
  • Ligands
  • Phenanthrenes
  • Retinoid X Receptors
  • Sesquiterpenes
  • dehydroabietic acid
  • isopimaric acid
  • valerenic acid