Generation and selection of novel estrogen receptor ligands using the de novo structure-based design tool, SkelGen

被引：29

作者：

Firth-Clark, S ^{[1
]}

Willems, HMG ^{[1
]}

Williams, A ^{[1
]}

Harris, W ^{[1
]}

机构：

[1] De Novo Pharmaceut Ltd, Cambridge CB4 9ZR, England

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2006年 / 46卷 / 02期

关键词：

D O I：

10.1021/ci0502956

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A de novo design approach to generating novel estrogen receptor (ER) ligands is described. The SkelGen program was used to generate ligands in the active sites of seven crystal structures of ER alpha. Seventeen high-scoring, diverse structures were selected from the SkelGen output and synthesized without introducing any modifications to the structures. Five ligands, four of which are novel, showed <= 25 mu M affinity, with the best compound displaying an IC50 of 340 nM. SkelGen can, therefore, be a powerful tool for designing active molecules.

引用

页码：642 / 647

页数：6

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