Development of a receptor-based 3D-QSAR study for the analysis of MMP2, MMP3, and MMP9 inhibitors
Development of a receptor-based 3D-QSAR study for the analysis of MMP2, MMP3, and MMP9 inhibitors
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DOI：
10.1016/j.bmc.2008.07.004
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发表时间：
2008-08-15
影响因子：
3.5
通讯作者：
Martinelli, Adriano
中科院分区：
文献类型：
--
作者：
Tuccinardi, Tiziano;Nuti, Elisa;Martinelli, Adriano
使用 MMP3 和 MMP8 评估 Gold 软件预测基质金属蛋白酶 (MMP) 抑制剂结合处置的能力。随后采用最佳程序将近 70 种化合物对接至 MMP2、MMP3 和 MMP9，测试其对三种 MMP 亚型的抑制活性。最佳结合姿势被用作 3D-QSAR 研究开发的对齐工具。对所得的三个 3D-QSAR 模型的评估使我们能够指出对活性和选择性很重要的配体特性和残基。 MMP2 是重要的抗癌药物靶点，而 MMP3 和 MMP9 被认为是肿瘤病理学的抗靶点。因此，我们的结果可以预测新 MMP2 抑制剂的结合亲和力，提供有关针对 MMP3 和 MMP9 的选择性的附加信息。此外，该策略也可用于其他 MMP 的研究。 (C) 2008 Elsevier Ltd. 保留所有权利。
The ability of Gold software to predict the binding disposition of matrix metalloproteinase (MMP) inhibitors was evaluated using MMP3 and MMP8. The best procedure was subsequently employed to dock into MMP2, MMP3 and MMP9 nearly 70 compounds that were tested for their inhibitory activity against the three MMP subtypes. The best binding poses were used as an alignment tool for the development of 3D-QSAR studies. Evaluation of the three resulting 3D-QSAR models allowed us to indicate the ligand properties and residues important for activity and selectivity. MMP2 is an important anticancer drug target, while MMP3 and MMP9 are considered to be anti-targets for tumor pathologies. As such, our results could predict the binding affinities of new MMP2 inhibitors, providing additional information regarding the selectivity against MMP3 and MMP9. Furthermore, this strategy may be used also for the investigation of other MMPs. (C) 2008 Elsevier Ltd. All rights reserved.