Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Iwashita, A., Hattori, K., Yamamoto, H., Ishida, J., Kido, Y., Kamijo, K., … Mutoh, S. (2005). Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors. FEBS Letters, 579(6), 1389–1393. https://doi.org/10.1016/j.febslet.2005.01.036