Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening
Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening
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DOI：
10.1021/jm7014777
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发表时间：
2008-06-12
影响因子：
7.3
通讯作者：
Keseru, Gyoergy M.
中科院分区：
文献类型：
--
作者：
Kiss, Robert;Kiss, Bela;Keseru, Gyoergy M.
在人组胺H4受体(HH4R)配体支持的同源模型上进行了基于结构的虚拟筛选(SBVS)。通过使用Flexx对接到hH4R结合位点，研究了来自不同供应商数据库的超过870万个3D结构。通过放射性配基结合分析，共筛选出255个化合物，其中16个化合物具有显著的[H-3]组胺置换。我们发现了几种新型的支架材料，可以用来开发未来的选择性H4配体。据我们所知，这是H4R上报道的第一个SBVS，代表着通过对虚拟命中的生物评估验证的最大虚拟屏幕之一。
A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were tested by radioligand binding assay and 16 of them possessed significant [H-3]histamine displacement. Several novel scaffolds were identified that can be used to develop selective H4 ligands in the future. As far as we know, this is the first SBVS reported on H4R, representing one of the largest virtual screens validated by the biological evaluation of the virtual hits.