计算性药物重新利用：方法、虚拟资源评估及案例研究

Computational drug repurposing: approaches, evaluation of in silico resources and case studies.

作者信息

Tanoli Ziaurrehman, Fernández-Torras Adrià, Özcan Umut Onur, Kushnir Aleksandr, Nader Kristen Michelle, Gadiya Yojana, Fiorenza Laura, Ianevski Aleksandr, Vähä-Koskela Markus, Miihkinen Mitro, Seemab Umair, Leinonen Henri, Seashore-Ludlow Brinton, Tampere Marianna, Kalman Adelinn, Ballante Flavio, Benfenati Emilio, Saunders Gary, Potdar Swapnil, Gómez García Ismael, García-Serna Ricard, Talarico Carmine, Beccari Andrea Rosario, Schaal Wesley, Polo Andrea, Costantini Susan, Cabri Enrico, Jacobs Marc, Saarela Jani, Budillon Alfredo, Spjuth Ola, Östling Päivi, Xhaard Henri, Quintana Jordi, Mestres Jordi, Gribbon Philip, Ussi Anton E, Lo Donald C, de Kort Martin, Wennerberg Krister, Fratelli Maddalena, Carreras-Puigvert Jordi, Aittokallio Tero

机构信息

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

出版信息

Nat Rev Drug Discov. 2025 Mar 18. doi: 10.1038/s41573-025-01164-x.

DOI:10.1038/s41573-025-01164-x

PMID:40102635

Abstract

Repurposing of existing drugs for new indications has attracted substantial attention owing to its potential to accelerate drug development and reduce costs. Hundreds of computational resources such as databases and predictive platforms have been developed that can be applied for drug repurposing, making it challenging to select the right resource for a specific drug repurposing project. With the aim of helping to address this challenge, here we overview computational approaches to drug repurposing based on a comprehensive survey of available in silico resources using a purpose-built drug repurposing ontology that classifies the resources into hierarchical categories and provides application-specific information. We also present an expert evaluation of selected resources and three drug repurposing case studies implemented within the Horizon Europe REMEDi4ALL project to demonstrate the practical use of the resources. This comprehensive Review with expert evaluations and case studies provides guidelines and recommendations on the best use of various in silico resources for drug repurposing and establishes a basis for a sustainable and extendable drug repurposing web catalogue.

摘要

将现有药物用于新适应症因其具有加速药物开发和降低成本的潜力而备受关注。已经开发了数百种计算资源，如数据库和预测平台，可用于药物再利用，这使得为特定的药物再利用项目选择合适的资源具有挑战性。为了帮助应对这一挑战，我们在此基于对现有计算机资源的全面调查，概述药物再利用的计算方法，该调查使用了专门构建的药物再利用本体，将资源分类为层次类别并提供特定应用信息。我们还对选定资源进行了专家评估，并介绍了在欧洲地平线REMEDi4ALL项目中实施的三个药物再利用案例研究，以展示这些资源的实际应用。这篇带有专家评估和案例研究的全面综述提供了关于如何最佳利用各种计算机资源进行药物再利用的指导方针和建议，并为可持续和可扩展的药物再利用网络目录奠定了基础。