Scaffold-Hopping from Synthetic Drugs by Holistic Molecular Representation.

ABSTRACT: The discovery of novel ligand chemotypes allows to explore uncharted regions in chemical space, thereby potentially improving synthetic accessibility, potency, and the drug-likeness of molecules. Here, we demonstrate the scaffold-hopping ability of the new Weighted Holistic Atom Localization and Entity Shape (WHALES) molecular descriptors compared to seven state-of-the-art molecular representations on 30,000 compounds and 182 biological targets. In a prospective application, we apply WHALES to the discovery of novel retinoid X receptor (RXR) modulators. WHALES descriptors identified four agonists with innovative molecular scaffolds, populating uncharted regions of the chemical space. One of the agonists, possessing a rare non-acidic chemotype, revealed high selectivity on 12 nuclear recept

SUBMITTER: Grisoni F 

PROVIDER: S-EPMC6220272 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature