胃癌（GC）被认为是癌症相关死亡的第四大原因和世界上第五大主要癌症，这是对全球公共健康的严重威胁。早期检测标志物的缺乏导致了迟到的诊断，即癌症的最后阶段，这可能与治疗策略的无效性有关，并且自然地导致了不良预后。尽管开发了各种治疗方法，但由于市场上可用药物的令人担忧的副作用，研究传统草药的趋势在增长。在这项研究中，使用50个具有抗胃癌活性的化合物（在先前的研究中已报道了IC50）创建了药效团生成和三维定量构效关系（3D-QSAR）模型。基于三个最佳药效团假设，对一个包含183,885个化合物的数据库进行了虚拟筛选，以发现最佳的抗胃癌化合物。选择的化合物与三个蛋白质受体7BKG、4F5B和4ZT1进行分子对接，以研究这些配体与受体之间的分子间相互作用。最后，选择了21个得分范围为-13.366至-6.404 kcal/mol的得分最高的导向化合物，然后计算了这些化合物的ADME/毒性属性。所有这些化合物的适应度得分均高于1.8，分子量小于500 g/mol，氢键供体最多为3，氢键受体最多为8.50，logP为1.013至4.174。最后，对得分最高的配体-受体复合物进行了分子动力学模拟。在数据库的183,885个化合物中，这些所选的导向化合物具有最强的抗胃癌效果。因此，未来的研究中可以考虑将这些导向化合物用于胃癌治疗。© 2023. 作者，特许给德黑兰大学医学科学。

Gastric cancer (GC) is known as the fourth leading cause of cancer-related death and the fifth major cancer in the world, and this is a serious threat to general health all over the world. The lack of early detection markers results in a belated diagnosis, i.e. the final stages, which could be associated with the ineffectiveness of the treatment strategies, and naturally, it leads to poor prognosis. Even though a variety of treatments have been developed, there is a trend of studying traditional medicinal plants, due to the worrying side effect of drugs available in the market.In this study, pharmacophore generation and 3D-QSAR model were created using 50 compounds with anti-gastric cancer activity (with IC50 had been reported in the previous studies).Based on three of the best pharmacophoric hypotheses, virtual screening was performed to discover the top anti-gastric cancer compounds from a database of 183,885 compounds. The selected compounds were used for molecular docking with three protein receptors 7BKG, 4F5B, and 4ZT1 to investigate the intermolecular interactions between these ligands and receptors. Finally, 21 lead compounds with the highest amount of docking score ranging from - 13.366 to -6.404 kcal/mol were selected, and then the ADME/Tox properties of these compounds were calculated. All these compounds have a fitness score above 1.8, a molecular weight of less than 500 g/mol, hydrogen bond donors up to 3, hydrogen bond acceptors up to 8.50, and logP of 1.013 to 4.174. Finally, molecular dynamic simulations for top-scoring ligand-receptor complexes were investigated.These selected lead compounds have the most anti-gastric cancer effects among the 183,885 compounds in the database. Therefore, lead compounds might be considered for gastric cancer therapy in future studies.© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.