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.
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Acknowledgements
The authors thank authors of the resources who have made their data and tools publicly available. They thank J. Tang for his valuable suggestions when conducting the survey. This work was supported by the REMEDi4ALL project, which has received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement No. 101057442. Views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union, who cannot be held responsible for them. Other funding sources include the Research Council of Finland (grant 351507 to Z.T. and grants 345803 and 340141 to T.A.) and Cancer Society of Finland (grants 4709137 and 4706788 to T.A.). For questions about the web catalogue, resource annotations, expert survey or the user guide, please contact Z.T. (ziaurrehman.tanoli@helsinki.fi).
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Development of the repurposing ontology: Z.T. Implementation of the online catalogue website: A.K., Z.T., T.A. Data analysis: Z.T, A.F.-T., U.O.Ö., L.F., Y.G., R.G.-S., J.C.-P., T.A. Demonstrator use cases: Z.T., A.F.-T., A.B., O.S., P.G., D.C.L., Y.G., P.Ö., J.Q., J.C.-P., M.F., L.F., B.S.-L., M.T., A.K., T.A. User guide for the top-15 resources: Z.T., K.M.N., U.O.Ö., L.F., M.V.-K., U.S., M.M., A.I., T.A. Annotations of the resources in the web catalogue: Z.T., M.V.-K., U.S., M.F., J.Q., T.A. Evaluation of the resources: Z.T., A.F.-T., M.V.-K., M.d.K., A.I., Y.G., P.G., O.S., U.S., H.L., M.F., L.F., J.Q., J.C.-P., T.A., M.M., K.W., H.X., A.E.U., B.S.-L., W.S., F.B., E.B., S.P., J.S., A.P., M.J., S.C., I.G.G., T.C., A.R.B. Leading the survey implementation: Z.T. and T.A. Figures: Z.T., A.F.-T., U.O.Ö., K.M.N. Drafting the manuscript: Z.T., A.F.-T., M.F., J.Q., J.C.-P., M.d.K., K.W., T.A. All the authors read and approved the final version.
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A.F.-T., I.G.G., R.G.-S., J.Q. and J.M. are employees of Chemotargets, a partner of the REMEDi4ALL project. ClarityVista is a software platform developed by Chemotargets. J.C.-P. and O.S. declare ownership in Phenaros Pharmaceuticals AB. T.C. and A.R.B. are employees of Dompé farmaceutici SpA, a partner of the REMEDi4ALL project. All the other authors declare no competing interests.
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Related links
ChatGPT-4: https://openai.com/index/gpt-4/
ClinGen: https://clinicalgenome.org
ClinicalTrials: clinicaltrials.gov
Cure ID: https://cure.ncats.io/home
Drug Interaction Checker: https://go.drugbank.com/drug-interaction-checker
Drug Repurposing Central: https://drugrepocentral.scienceopen.com/collection/fee38437-df5d-4641-bd7f-b1b61882cd75
FinnGen: https://www.finngen.fi/en
Genebass: https://app.genebass.org
GTEx: https://gtexportal.org/home/
Human Cell Atlas: https://www.humancellatlas.org
In-silico Drug Repurposing Catalogue - REMEDi4ALL: https://remedi4all.org/in-silico-drug-repurposing-catalogue/
Orphanet: https://www.orpha.net
PheWAS Portal: https://azphewas.com
PubMed: https://pubmed.ncbi.nlm.nih.gov/
REMEDi4ALL project: https://remedi4all.org/
Sage Bionetworks: https://sagebionetworks.org
UK Biobank: https://www.ukbiobank.ac.uk
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Tanoli, Z., Fernández-Torras, A., Özcan, U.O. et al. Computational drug repurposing: approaches, evaluation of in silico resources and case studies. Nat Rev Drug Discov 24, 521–542 (2025). https://doi.org/10.1038/s41573-025-01164-x
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DOI: https://doi.org/10.1038/s41573-025-01164-x
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