Gil-Pichardo Alberto, Sánchez-Ruiz Andrés, Colmenarejo Gonzalo
Biostatistics and Bioinformatics Unit, IMDEA Food, CEI UAM+CSIC, 28049, Madrid, Spain.
J Cheminform. 2023 Oct 13;15(1):96. doi: 10.1186/s13321-023-00768-y.
Gut-targeted drugs provide a new drug modality besides that of oral, systemic molecules, that could tap into the growing knowledge of gut metabolites of bacterial or host origin and their involvement in biological processes and health through their interaction with gut targets (bacterial or host, too). Understanding the properties of gut metabolites can provide guidance for the design of gut-targeted drugs. In the present work we analyze a large set of gut metabolites, both shared with serum or present only in gut, and compare them with oral systemic drugs. We find patterns specific for these two subsets of metabolites that could be used to design drugs targeting the gut. In addition, we develop and openly share a Super Learner model to predict gut permanence, in order to aid in the design of molecules with appropriate profiles to remain in the gut, resulting in molecules with putatively reduced secondary effects and better pharmacokinetics.
肠道靶向药物提供了一种除口服全身作用分子之外的新药物形式，它可以利用对细菌或宿主来源的肠道代谢物及其通过与肠道靶点（细菌或宿主）相互作用参与生物过程和健康的认识。了解肠道代谢物的特性可为肠道靶向药物的设计提供指导。在本研究中，我们分析了大量的肠道代谢物，包括与血清共有的或仅存在于肠道中的，并将它们与口服全身作用药物进行比较。我们发现了这两类代谢物的特定模式，可用于设计靶向肠道的药物。此外，我们开发并公开分享了一个超级学习模型来预测肠道滞留性，以帮助设计具有适当特征的分子以留在肠道中，从而产生具有假定减少的副作用和更好药代动力学的分子。
