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

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 performed. 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 low molecular chemical compounds, 9 PARP1 inhibitors were revealed; the most active ones, namely, STK031481, STK056130, and STK265022, displayed biological effect at a micromolar concentration (IC 50 = 2.0, 1.0, and 2.6 μM, respectively).