TY - JOUR T1 - Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors. AU - Iwashita,Akinori, AU - Hattori,Kouji, AU - Yamamoto,Hirofumi, AU - Ishida,Junya, AU - Kido,Yoshiyuki, AU - Kamijo,Kazunori, AU - Murano,Kenji, AU - Miyake,Hiroshi, AU - Kinoshita,Takayoshi, AU - Warizaya,Masaichi, AU - Ohkubo,Mitsuru, AU - Matsuoka,Nobuya, AU - Mutoh,Seitaro, PY - 2005/01/03/received PY - 2005/01/17/revised PY - 2005/01/17/accepted PY - 2005/3/1/pubmed PY - 2005/4/2/medline PY - 2005/3/1/entrez SP - 1389 EP - 93 JF - FEBS letters JO - FEBS Lett VL - 579 IS - 6 N2 - 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. SN - 0014-5793 UR - https://www.unboundmedicine.com/medline/citation/15733846/Discovery_of_quinazolinone_and_quinoxaline_derivatives_as_potent_and_selective_poly_ADP_ribose__polymerase_1/2_inhibitors_ DB - PRIME DP - Unbound Medicine ER -