Reviewing ligand-based rational drug design: the search for an ATP synthase inhibitor

Int J Mol Sci. 2011;12(8):5304-18. doi: 10.3390/ijms12085304. Epub 2011 Aug 17.

Abstract

Following major advances in the field of medicinal chemistry, novel drugs can now be designed systematically, instead of relying on old trial and error approaches. Current drug design strategies can be classified as being either ligand- or structure-based depending on the design process. In this paper, by describing the search for an ATP synthase inhibitor, we review two frequently used approaches in ligand-based drug design: The pharmacophore model and the quantitative structure-activity relationship (QSAR) method. Moreover, since ATP synthase ligands are potentially useful drugs in cancer therapy, pharmacophore models were constructed to pave the way for novel inhibitor designs.

Keywords: ATP synthase ligands; pharmacophore; quantitative structure-activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Binding Sites
  • Drug Design*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Ligands*
  • Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors
  • Mitochondrial Proton-Translocating ATPases / chemistry*
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Subunits
  • Quantitative Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Ligands
  • Protein Subunits
  • Mitochondrial Proton-Translocating ATPases