We present a Focused Library Generator that is able to create from scratch new molecules with desired properties. After training the Generator on the ChEMBL database, transfer learning was used to switch the generator to producing new Mdmx inhibitors that are a promising class of anticancer drugs. Lilly medicinal chemistry filters, molecular docking, and a QSAR IC₅₀ model were used to refine the output of the Generator. Pharmacophore screening and molecular dynamics (MD) simulations were then used to further select putative ligands. Finally, we identified five promising hits with equivalent or even better predicted binding free energies and IC₅₀ values than known Mdmx inhibitors. The source code of the project is available on https://github.com/bigchem/online-chem.

我们提出了一个聚焦库生成器，它能够从头开始创建具有所需特性的新分子。在 ChEMBL 数据库上训练生成器后，使用迁移学习将生成器转换为生产新的 Mdmx 抑制剂，这是一类有前途的抗癌药物。Lilly 药物化学过滤器、分子对接和 QSAR IC ₅₀模型用于改进 Generator 的输出。然后使用药效团筛选和分子动力学 (MD) 模拟进一步选择推定的配体。最后，我们确定了与已知 Mdmx 抑制剂相当甚至更好的预测结合自由能和 IC ₅₀值的五个有希望的命中。该项目的源代码可在 https://github.com/bigchem/online-chem 上获得。