Related Experiment Video
Updated: Sep 29, 2026

Visualization and Quantitative Analysis of Genotoxin-Induced PARP1/PARP2 Activation in Cells Using a Fluorescent Fusion Protein-Based Reporter
Published on: April 17, 2026
Substituted uracil derivatives as potent inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)
Henning Steinhagen1, Michael Gerisch, Joachim Mittendorf
1Institute of Medicinal Chemistry, Pharma Research Centre, Bayer AG, D-42096, Wuppertal, FRG . henning.steinhagen@aventis.com
Abstract:
A new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC(50)=2microM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (IC(50)<20nM). Additionally, physicochemical and pharmacokinetic properties were evaluated. It could be shown that compounds bearing a piperazine or phenyl substituted betaAla-Gly side chain exhibited the best overall profile.
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