437998-61-3Relevant academic research and scientific papers
Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling
Ishida, Junya,Yamamoto, Hirofumi,Kido, Yoshiyuki,Kamijo, Kazunori,Murano, Kenji,Miyake, Hiroshi,Ohkubo, Mitsuru,Kinoshita, Takayoshi,Warizaya, Masaichi,Iwashita, Akinori,Mihara, Kayoko,Matsuoka, Nobuya,Hattori, Kouji
, p. 1378 - 1390 (2007/10/03)
We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinant PARP-1 and PARP-2, the quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2, and the quinazolidinone derivatives did not have selectivity for PARP-1/2. Structure-based drug design analysis via a combination of X-ray structural study utilizing the complexes of inhibitors and human PARP-1 catalytic domain, and homology modeling using murine PARP-2 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.
