Multidimensional de novo design reveals 5-HT2B receptor-selective ligands.

Journal Article (Journal Article)

We report a multi-objective de novo design study driven by synthetic tractability and aimed at the prioritization of computer-generated 5-HT2B receptor ligands with accurately predicted target-binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand-efficient 5-HT2B modulators with sustained cell-based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics-assisted synthesis enables the swift generation of small molecules with the desired polypharmacology.

Full Text

Duke Authors

Cited Authors

  • Rodrigues, T; Hauser, N; Reker, D; Reutlinger, M; Wunderlin, T; Hamon, J; Koch, G; Schneider, G

Published Date

  • January 2015

Published In

Volume / Issue

  • 54 / 5

Start / End Page

  • 1551 - 1555

PubMed ID

  • 25475886

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

International Standard Serial Number (ISSN)

  • 1433-7851

Digital Object Identifier (DOI)

  • 10.1002/anie.201410201

Language

  • eng