Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis
Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis
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DOI：
10.1016/j.bmcl.2007.04.095
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发表时间：
2007-07-15
影响因子：
2.7
通讯作者：
Selwood, David L.
中科院分区：
文献类型：
--
作者：
Hartzoulakis, Basil;Rossiter, Sharon;Selwood, David L.
描述了一种用于发现DDAH酶抑制剂的有效方法，而不需要高通量筛选。根据药物相似性对308，000种化合物文库进行物理化学过滤，然后进行倒数最近邻选择，产生了35，000种化合物的代表性子集。使用FlexX在双处理器PC上进行虚拟筛选，然后进行生物筛选，确定了两个命中系列。商业数据库的相似性搜索和纯化合物的化学再合成导致SR 445作为铜绿假单胞菌DDAH的抑制剂，浓度为2 μ M。(C)2007爱思唯尔有限公司保留所有权利。
An efficient process for the discovery of inhibitors of DDAH enzymes, without the requirement for high throughput screening, is described. Physicochemical filtering of a 308,000-compound library according to drug likeness followed by reciprocal nearest neighbour selection produced a representative subset of 35,000 compounds. Virtual screening on a dual processor PC using FlexX, followed by biological screening, identified two hit series. Similarity searches of commercial databases and chemical re-synthesis of pure compounds resulted in SR445 as an inhibitor of Pseudomonas aeruginosa DDAH at 2 mu M. (C) 2007 Elsevier Ltd. All rights reserved.