II 型糖尿病最常用的一线治疗药物是二甲双胍。最近的报告声称，这种糖尿病药物还可以保护使用者免受癌症的侵害。二甲双胍诱导癌细胞的细胞周期停滞。然而，癌症系统中发生这种情况的确切机制尚未阐明。在这里，我们利用转化生长因子 (TGF)-β 途径研究了二甲双胍对癌细胞细胞周期停滞的影响。 TGF-β途径对细胞进展和生长具有显着影响。为了深入了解二甲双胍对 TGF β 受体 1 激酶影响的潜在分子机制，进行了分子对接。根据分子对接和分子动力学模拟，预计二甲双胍会与转化生长因子 (TGF)-β 受体 I 激酶相互作用。此外，还为二甲双胍-TGF-ßR1复合物生成了药效团，以寻找与二甲双胍具有相似药效团并具有增强抗癌潜力的新型化合物。对 Ligandscout® 软件中生成的药效团分别使用 NPASS 数据库中的 29,000 种天然化合物进行虚拟筛选。药效团图谱显示二甲双胍-TGF-ßR1 复合物有 60 种先导化合物。对这些化合物进行了分子对接、100 ns 分子动力学模拟和 ADMET 分析。 CID 72473、10316977 和 45140078 的化合物显示出良好的结合亲和力，并在与上述蛋白质的动力学模拟过程中形成稳定的复合物，因此具有开发成抗癌药物的潜力。版权：© 2023 Reza 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The most frequently prescribed first-line treatment for type II diabetes mellitus is metformin. Recent reports asserted that this diabetes medication can also shield users from cancer. Metformin induces cell cycle arrest in cancer cells. However, the exact mechanism by which this occurs in the cancer system is yet to be elucidated. Here, we investigated the impact of metformin on cell cycle arrest in cancer cells utilizing transforming growth factor (TGF)-beta pathway. TGF-ß pathway has significant effect on cell progression and growth. In order to gain an insight on the underlying molecular mechanism of metformin's effect on TGF beta receptor 1 kinase, molecular docking was performed. Metformin was predicted to interact with transforming growth factor (TGF)-beta receptor I kinase based on molecular docking and molecular dynamics simulations. Furthermore, pharmacophore was generated for metformin-TGF-ßR1 complex to hunt for novel compounds having similar pharmacophore as metformin with enhanced anti-cancer potentials. Virtual screening with 29,000 natural compounds from NPASS database was conducted separately for the generated pharmacophores in Ligandscout® software. Pharmacophore mapping showed 60 lead compounds for metformin-TGF-ßR1 complex. Molecular docking, molecular dynamics simulation for 100 ns and ADMET analysis were performed on these compounds. Compounds with CID 72473, 10316977 and 45140078 showed promising binding affinities and formed stable complexes during dynamics simulation with aforementioned protein and thus have potentiality to be developed into anti-cancer medicaments.Copyright: © 2023 Reza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.