Integrating virtual screening in lead discovery. Academic Article Review uri icon

start page

  • 349

end page

  • 358

abstract

  • Target- and ligand-based virtual screening have emerged as resource-saving techniques that have been successfully applied to identify novel chemotypes in biologically active molecules. Eight confirmed virtual screening hits have recently been described and are discussed in this review, with focus on the workflow. These are then evaluated in the light of pharmacokinetics prediction (e.g. Caco-2 permeability, cytochrome P450 inhibition and hERG binding). We anticipate problems for five of these hits (e.g. cardiac toxicity), which warrant further experiments. Future challenges include dynamic tautomer/protonation treatment for both ligands and targets and improved pre- and post- virtual screening filters.

date/time value

  • 2004

Digital Object Identifier (DOI)

  • 10.1016/j.cbpa.2004.06.008

PubMed Identifier

  • 15288243

volume

  • 8

number

  • 4

keywords

  • Animals
  • Computer-Aided Design
  • Databases, Factual
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Ligands
  • Molecular Structure
  • Structure-Activity Relationship