Drug Res (Stuttg) 2023; 73(09): 481-490
DOI: 10.1055/a-2095-0826

Repurposing Drugs: An Empowering Approach to Drug Discovery and Development

Drug repurposing for drug development
1   Pharmacology, ESIC Dental College and Hospital, New Delhi, India
Vandana Roy
2   Pharmacology, Maulana Azad Medical College, New Delhi, India
› Author Affiliations


Drug discovery and development is a time-consuming and costly procedure that necessitates a substantial effort. Drug repurposing has been suggested as a method for developing medicines that takes less time than developing brand new medications and will be less expensive. Also known as drug repositioning or re-profiling, this strategy has been in use from the time of serendipitous drug discoveries to the modern computer aided drug designing and use of computational chemistry. In the light of the COVID-19 pandemic too, drug repurposing emerged as a ray of hope in the dearth of available medicines. Data availability by electronic recording, libraries, and improvements in computational techniques offer a vital substrate for systemic evaluation of repurposing candidates. In the not-too-distant future, it could be possible to create a global research archive for us to access, thus accelerating the process of drug development and repurposing. This review aims to present the evolution, benefits and drawbacks including current approaches, key players and the legal and regulatory hurdles in the field of drug repurposing. The vast quantities of available data secured in multiple drug databases, assisting in drug repurposing is also discussed.

Publication History

Received: 31 January 2023

Accepted: 09 May 2023

Article published online:
21 July 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Mohs RC, Greig NH. Drug discovery and development: Role of basic biological research. Alzheimers Dement (N Y) 2017; 3: 651-657
  • 2 Weng L, Zhang L, Peng Y. et al. Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics 2013; 14: 315-324
  • 3 Sam E, Athri P. Web-based drug repurposing tools: a survey. Brief Bioinform 2019; 20: 299-316
  • 4 Naylor S, Schonfeld JM. Therapeutic Drug Repurposing, Repositioning and Rescue – Part 1: Overview Drug Discovery World Winter 2014/15 49.
  • 5 US Food and Drug Administration. The drug development process: Step 1: Discovery and development. 4 January 2018. Retrieved 18 December. 2019
  • 6 Rivera SM, Gilman AG. Drug Invention and the Pharmaceutical Industry. Chapter-1 In : Brunton LL (ed). Goodman Gilman’s The Pharmacological Basis of Therapeutics. 12th Edition. McGraw Hill Education; 2011: 3-16
  • 7 Camfield DA, Stough C, Farrimond J. et al. Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis. Nutrition Reviews 2014; 72: 507-522
  • 8 Pesta DH, Angadi SS, Burtscher M. et al. The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance. Nutrition & Metabolism 2013; 10: 71
  • 9 Bledsoe BE, Porter RS, Cherry RA. Chapter-3 Intermediate Emergency Care. Upper Saddle River. NJ: Pearson Prentice Hill 2004; 260
  • 10 Brown JH, Laiken N. Muscarinic Receptor Agonists and Antagonists. Chapter-9 In : Brunton LL (ed). Goodman Gilman’s The Pharmacological Basis of Therapeutics. 12th Edition. McGraw Hill Education; 2011. 233.
  • 11 Elhadef K, Smaoui S, Fourati M. et al. A Review on Worldwide Ephedra History and Story: From Fossils to Natural Products Mass Spectroscopy Characterization and Biopharmacotherapy Potential. Evid Based Complement Alternat Med 2020; 2020: 1540638
  • 12 Statler AK, Maani CV, Kohli A. Ephedrine. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547661/
  • 13 Burr SA, Leung YL. Encyclopedia of Toxicology (Third Edition) 2014; 1088-1108
  • 14 Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc 2012; 87: 982-990
  • 15 Tabarrok AT. Assessing the FDA via the anomaly of off-label drug prescribing. Indep Rev 2000; 5: 25-53
  • 16 Stone KJ, Viera AJ, Parman CL. Off-Label Applications for SSRIs. Am Fam Physician 2003; 68: 498-504
  • 17 Rigopoulos P, Dardalas I, Pourzitaki C. Emphasis on the off-label use of methotrexate for ectopic pregnancy. Am J Obstet Gynecol 2019; 220: 611-612
  • 18 Maneeton N, Maneeton B, Srisurapanont M. et al. Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials. Psychiatry Clin Neurosci 2011; 65: 611-617
  • 19 Lage OM, Ramos MC, Calisto R. et al. Current Screening Methodologies in Drug Discovery for Selected Human Diseases. Mar Drugs 2018; 16: 279
  • 20 Shim JS, Liu JO. Recent advances in drug repositioning for the discovery of new anticancer drugs. Int J Biol Sci 2014; 10: 654-663
  • 21 Volberding PA, Lagakos SW, Koch MA. et al. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N Engl J Med 1990; 322: 941-949
  • 22 Regueira TB, Kildegaard KR, Hansen BG. et al. Molecular basis for mycophenolic acid biosynthesis in Penicillium brevicompactum. Appl Environ Microbiol 2011; 77: 3035-3043
  • 23 Cornillie F. Ten years of infliximab (remicade) in clinical practice: the story from bench to bedside. Eur J Pharmacol 2009; 623: S1-4
  • 24 Meyerhoff A. U. S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis Clin. Infect. Dis. 28 1999; 42-48
  • 25 Tan KR, Magill AJ, Parise ME. et al. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg 2011; 84: 517-531
  • 26 Simarro PP, Franco J, Diarra A. et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012; 139: 842-846
  • 27 Smorenburg CH, Seynaeve C, Bontenbal M. et al. Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients. Anti-Cancer Drugs 2000; 11: 825-828
  • 28 Ben Salah A, Ben Messaoud N, Guedri E. et al. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med 2013; 368: 524-532
  • 29 Beigel JH, Tomashek KM, Dodd LE. et al. ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 – Final Report. N Engl J Med 2020; 383: 1813-1826
  • 30 Rodrigues L, Bento Cunha R, Vassilevskaia T. et al. Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates. Molecules. 2022; 27: 2723
  • 31 Dudley JT, Deshpande T, Butte AJ. Exploiting drug–disease relationships for computational drug repositioning. Brief Bioinform 2011; 12: 303-311
  • 32 Novac N. Challenges and opportunities of drug repositioning. Trends Pharmacol Sci 2013; 34: 267-272
  • 33 Padhy B, Gupta Y. Drug repositioning: re-investigating existing drugs for new therapeutic indications. J Postgrad Med 2011; 57: 153
  • 34 Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 2004; 3: 673-683
  • 35 Ye H, Liu Q, Wei J. Construction of drug network based on side effects and its application for drug repositioning. PLoS One 2014; 9: e87864
  • 36 Li YY, Jones SJ. Drug repositioning for personalized medicine. Genome Med 2012; 4: 27
  • 37 Oprea TI, Bauman JE, Bologa CG. et al. Drug Repurposing from an Academic Perspective. Drug Discovery Today: Therapeutic Strategies 2011; 8: 61-69
  • 38 Cha Y, Erez T, Reynolds IJ. et al. Drug repurposing from the perspective of pharmaceutical companies. Br J Pharmacol 2018; 175: 168-180
  • 39 DiMasi JA, Feldman L, Seckler A. et al. Trends in risks associated with new drug development: success rates for investigational drugs. Clin Pharmacol Ther 2010; 87: 272-277
  • 40 Firth A, Prathapan P. Broad-spectrum therapeutics: A new antimicrobial class. Current Research in Pharmacology and Drug Discovery 2021; 2: 100011 DOI: 10.1016/j.crphar.2020.100011.
  • 41 Buckley CE, Marguerie A, Roach AG. et al. Drug reprofiling using zebrafish identifies novel compounds with potential pro-myelination effects. Neuropharmacol 2010; 59: 149-159
  • 42 Deshmukh VA, Tardif V, Lyssiotis CA. et al. A regenerative approach to the treatment of multiple sclerosis. Nature 2013; 502: 327-350
  • 43 Mei F, Fancy SPJ, Shen YA. et al. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med 2014; 20: 954-960
  • 44 Najm FJ, Madhavan M, Zaremba A. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature 2015; 522: 216-235
  • 45 Lariosa-Willingham KD, Rosler ES, Tung JS. et al. A high throughput drug screening assay to identify compounds that promote oligodendrocyte differentiation using acutely dissociated and purified oligodendrocyte precursor cells. BMC Res Notes 2016; 9: 419-433
  • 46 Lotfi Shahreza M, Ghadiri N, Mousavi SR. et al. A review of network-based approaches to drug repositioning. Brief Bioinform 2018; 19: 878-892
  • 47 Morris GM, Lim-Wilby M. Molecular docking. In: A Kukol (ed). Molecular Modeling of Proteins. Totowa, NJ: Humana Press; 2008: 365-382
  • 48 Ding H, Takigawa I, Mamitsuka H. et al. Similarity-based machine learning methods for predicting drug-target interactions: a brief review. Brief Bioinform 2014; 15: 734-747
  • 49 Lamb J, Crawford ED, Peck D. et al. The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Science 2006; 313: 1929-1935
  • 50 Teachey DT, Sheen C, Hall J. et al. mTOR inhibitors are synergistic with methotrexate: an effective combination to treat acute lymphoblastic leukemia. Blood 2008; 112: 2020-2023
  • 51 Fransecky L, Mochmann LH, Baldus CD. Outlook on PI3K/AKT/mTOR inhibition in acute leukemia. Mol Cell Ther 2015; 3: 2-19
  • 52 Brilliant MH, Vaziri K, Connor TB. et al. Mining retrospective data for virtual prospective drug repurposing: L-DOPA and age-related macular degeneration. Am J Med 2016; 129: 292-298
  • 53 LeCun Y, Bengio Y, Hinton G. Deep learning. Nature 2015; 521: 436-444
  • 54 Meyer JG, Liu S, Miller IJ. et al. Learning drug functions from chemical structures with convolutional neural networks and random forests. J Chem Inf Model 2019; 59: 4438-4449
  • 55 Segler MHS, Kogej T, Tyrchan C. et al. Generating focused molecule libraries for drug discovery with recurrent neural networks. ACS Cent Sci 2018; 4: 120-131
  • 56 Beck BR, Shin B, Choi Y. et al. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput Struct Biotechnol J 2020; 18: 784-790
  • 57 Ge Y, Tian T, Huang S. et al, A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19. bioRxiv 2020; published online March 12 DOI: 10.1101/2020.03.11.986836. (preprint)
  • 58 Paik H, Chung AY, Park HC. et al. Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records. Sci Rep 2015; 5: 8580-8588
  • 59 Jiang Z, Zhou Y. Using gene networks to drug target identification. J Integr Bioinform 2005; 2: 14
  • 60 Zou J, Zheng MW, Li G. et al. Advanced systems biology methods in drug discovery and translational biomedicine. Biomed Res Int 2013; 2013: 8
  • 61 Allarakhia M. Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases. Drug Des Devel Ther 2013; 7: 753-766
  • 62 Zhu Y, Elemento O, Pathak J. et al. Drug knowledge bases and their applications in biomedical informatics research. Brief Bioinform 2019; 20: 1308-1321
  • 63 Gao Z, Li H, Zhang H. et al. PDTD: a web-accessible protein database for drug target identification. BMC Bioinformatics 2008; 9: 104
  • 64 Wang Y, Zhang S, Li F. et al. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res 2020; 48: D1031-D1041
  • 65 Whirl-Carrillo M, McDonagh EM, Hebert JM. et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2012; 92: 414-417 DOI: 10.1038/clpt.2012.96.. PMID: 22992668; PMCID: PMC3660037
  • 66 KEGG: Kyoto Encyclopedia of Genes and Genomes [Internet] [accessed on March 5, 2021] Available from: https://www.genome.jp/kegg/drug/
  • 67 Wishart DS, Knox C, Guo AC. et al, DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 36. D901-D906 DOI: 10.1093/nar/gkm958. Epub 2007 Nov 29 PMID: 18048412; PMCID: PMC2238889.
  • 68 SuperTarget: an extensive web resource for analyzing 332828 drug-target interactions. [Internet] [Accessed on March 5, 2021] Available from: https://bioinformatics.charite.de/supertarget/index.php?site=home
  • 69 US Food and Drug Administration. FDA/CDER SBIA Chronicles. Patents and Exclusivity. 2015 [Accessed on May 5, 2023] Available from: https://www.fda.gov/media/92548/download
  • 70 Breckenridge A, Jacob R. Overcoming the legal and regulatory barriers to drug repurposing. Nat Rev Drug Discov. 2019 18. 1-2 DOI: 10.1038/nrd.2018.92. Epub 2018 Jun 8 PMID: 29880920
  • 71 Talevi A, Bellera CL. Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics. Expert Opin Drug Discov 2020; 15: 397-401 DOI: 10.1080/17460441.2020.1704729.. Epub 2019 Dec 17 PMID: 31847616
  • 72 Walsh BS, Sarpatwari A, Rome BN. et al, Frequency of First Generic Drug Approvals With "Skinny Labels" in the United States. JAMA Intern Med. 2021: e210484 DOI: 10.1001/jamainternmed.2021.0484. Epub ahead of print PMID: 33779681; PMCID: PMC8008438
  • 73 Witkowski TX. Intellectual property and other legal aspects of drug repurposing. Drug Discovery Today: Therapeutic Strategies 2011; 8: 139-143