[Improved procedure of the search for poly(ADP-ribose) polymerase-1 potential inhibitors with use of molecular docking approach]

Mol Biol (Mosk). 2011 May-Jun;45(3):565-9.
[Article in Russian]

Abstract

A search for poly(ADP-ribose) polymerase-1 inhibitors by virtual screening of a chemical compound database and a subsequent experimental verification of their activities have been done. It was shown that the most efficient method to predict inhibitory properties implies a combinatorial approach joining molecular docking capabilities with structural filtration. Among more than 300000 database chemicals 9 PARP1 inhibitors were revealed; the most active ones, namely: STK031481, STK056130, and STK265022,--displayed biological effect at a micro-molar concentration (IC50 = 2.0 microM, 1.0 microM and 2.6 microM, respectively).

Publication types

  • English Abstract

MeSH terms

  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nucleic Acid Synthesis Inhibitors / chemistry*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Phthalazines / chemistry*
  • Phthalazines / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Small Molecule Libraries
  • Structure-Activity Relationship

Substances

  • Nucleic Acid Synthesis Inhibitors
  • Phthalazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Small Molecule Libraries