当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling.

Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling.

Abstract：

: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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Ishida J,Yamamoto H,Kido Y,Kamijo K,Murano K,Miyake H,Ohkubo M,Kinoshita T,Warizaya M,Iwashita A,Mihara K,Matsuoka N,Hattori K

doi

10.1016/j.bmc.2005.09.061

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

1378-90

issue

5

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(05)00941-7

journal_volume

14

pub_type

杂志文章

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