Download MendeleyDiscovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors.
Iwashita, A., Hattori, K., Yamamoto, H., Ishida, J., Kido, Y., Kamijo, K., Murano, K., Miyake, H., Kinoshita, T., Warizaya, M., Ohkubo, M., Matsuoka, N., Mutoh, S.(2005) FEBS Lett 579: 1389-1393
- PubMed: 15733846
- DOI: https://doi.org/10.1016/j.febslet.2005.01.036
- Primary Citation of Related Structures:
1WOK - PubMed Abstract:
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.
Organizational Affiliation:
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Osaka 532-8514, Japan. [email protected]
