Yu Hui, Wang Zhanli, Zhang Liangren, Zhang Jufeng, Huang Qian
Central Experimental Laboratory, The First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
Bioorg Med Chem Lett. 2007 Apr 15;17(8):2126-33. doi: 10.1016/j.bmcl.2007.01.089. Epub 2007 Feb 2.
In order to elucidate the essential structural features for KDR kinase inhibitors, three-dimensional pharmacophore hypotheses were built on the basis of a set of known KDR kinase inhibitors selected from the literature with CATALYST program. Several methods tools used in validation of pharmacophore hypothsis were presented, and the first hypothesis (Hypo1) was considered to be the best pharmacophore hypothesis. The model (Hypo1) was then employed as 3D search query to screen the Traditional Chinese Medicine Database (TCMD) for other potential lead compounds. One hit illustrated high binding affinity with KDR kinase measured by the surface plasmon resonance biosensor. Docking studies may help elucidate the mechanisms of KDR kinase receptor-ligand interactions.
为了阐明KDR激酶抑制剂的基本结构特征，基于从文献中选取的一组已知KDR激酶抑制剂，利用CATALYST程序构建了三维药效团假设。介绍了用于验证药效团假设的几种方法工具，并且第一个假设（Hypo1）被认为是最佳药效团假设。然后将该模型（Hypo1）用作三维搜索查询，以筛选中药数据库（TCMD）寻找其他潜在的先导化合物。通过表面等离子体共振生物传感器测得，有一个命中物显示出与KDR激酶的高结合亲和力。对接研究可能有助于阐明KDR激酶受体 - 配体相互作用的机制。
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