2. Academic Validation
  3. Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors

Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors

  • FEBS Lett. 2005 Feb 28;579(6):1389-93. doi: 10.1016/j.febslet.2005.01.036.
Akinori Iwashita 1,  Kouji Hattori,  Hirofumi Yamamoto,  Junya Ishida,  Yoshiyuki Kido,  Kazunori Kamijo,  Kenji Murano,  Hiroshi Miyake,  Takayoshi Kinoshita,  Masaichi Warizaya,  Mitsuru Ohkubo,  Nobuya Matsuoka,  Seitaro Mutoh
Affiliations

Affiliation

  • 1 Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Osaka 532-8514, Japan. [email protected]
PMID: 15733846 DOI: 10.1016/j.febslet.2005.01.036
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.

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