Korean Ginseng Center and Ginseng Genetic Resource Bank, Kyung Hee University, Yongin 449-701, Republic of Korea.
Comput Biol Med. 2013 Jul;43(6):786-97. doi: 10.1016/j.compbiomed.2013.02.020. Epub 2013 Apr 30.
Natural products have served as structural resources in the history of drug discovery for cancer therapy. Among these natural products, Korean Panax ginseng serves as a potential anti-cancer medicinal plant. To determine the anti-cancer activities of Korean P. ginseng active compounds, we performed pharmacophore-based virtual screening and molecular docking studies on EGFR (epidermal growth factor receptor) tyrosine kinase domain. The EGFR family tyrosine kinase receptor is a cell surface receptor that regulates diverse biological processes including cell proliferation, differentiation, survival, and apoptosis. Over expression of EGFR tyrosine kinase domain associated with the development and progression of numerous human cancers. In our study, we developed the best pharmacophore model (Hypo1) using a diverse training set and validated by Fischer's randomization, a test set, and a decoy set. The best validated model was employed in the virtual screening of P. ginseng compound database. Further, chosen molecules were evaluated by applying ADMET screening and molecular docking studies. Finally, 14 compounds were obtained based on binding affinity scores and interactions with protein active site residues. These final lead compounds from P. ginseng can be used in the designing of new EGFR tyrosine kinase inhibitors.
天然产物在癌症治疗药物发现的历史中一直是结构资源。在这些天然产物中，韩国人参被认为是一种有潜力的抗癌药用植物。为了确定韩国人参活性化合物的抗癌活性，我们对表皮生长因子受体（EGFR）酪氨酸激酶结构域进行了基于药效团的虚拟筛选和分子对接研究。EGFR 家族酪氨酸激酶受体是一种细胞表面受体，调节包括细胞增殖、分化、存活和凋亡在内的多种生物学过程。EGFR 酪氨酸激酶结构域的过度表达与许多人类癌症的发生和发展有关。在我们的研究中，我们使用多种训练集开发了最佳药效团模型（Hypo1），并通过 Fischer 随机化、测试集和诱饵集进行了验证。最佳验证模型用于人参化合物数据库的虚拟筛选。此外，还通过应用 ADMET 筛选和分子对接研究对选定的分子进行了评估。最后，根据结合亲和力评分和与蛋白质活性位点残基的相互作用，获得了 14 种化合物。这些来自人参的最终先导化合物可用于设计新型 EGFR 酪氨酸激酶抑制剂。
