Login Register Cart 0
Generic placeholder image

Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Drug Repositioning: A Unique Approach to Refurbish Drug Discovery

Author(s): Mayura A. Kale*, Prashant B. Shamkuwar, Vishnukant K. Mourya, Aishwarya B. Deshpande and Priyanka A. Shelke

Volume 19, Issue 1, 2022

Published on: 16 March, 2021

Article ID: e140122192307 Pages: 8

DOI: 10.2174/1570163818666210316114331

Price: $65

Abstract

For a decade, it has been observed that there is a remarkable decrease in the quantum of novel clinically approved drugs, in spite of modernization in the research and development process. We have highlighted repositioning of drugs as a methodology that has found new therapeutic implications for clinically approved drugs but with different indications. This can be considered as an upbringing strategy to deliver timely and cost-effective solutions, which still need exploration for getting over the shortage of novel drugs reaching the market. This review focuses on an activity-based drug repositioning approach, which is used to explore new uses of known drugs that are already approved for specific indications and are now being used for other indications on the basis that a single drug interacts with multiple targets. It also includes current research trends related to drug repositioning, which depends on strong knowledge of medicinal chemistry and involves elucidation of mechanisms of action and validation of novel targets. The review highlights the importance of computational tools and databases of various forms for drug repositioning purposes, which have enhanced the ability to pose reasonable and testable hypotheses. The critical nature of this aspect is obvious in cases where data gathered from in vitro, or animal models do not confirm in subsequent clinical trials. Hence, considering the positive outcomes of drug repositioning, it can be surmised that this approach can serve as a promising one that can develop into a robust drug discovery strategy.

Keywords: Drug repositioning, computational tools, databases, drug discovery, medicinal chemistry, drug targets.

Graphical Abstract

[1]
Shameer K, Readhead B, Dudley JT. Computational and experimental advances in drug repositioning for accelerated therapeutic stratification. Curr Top Med Chem 2015; 15(1): 5-20.
[http://dx.doi.org/10.2174/1568026615666150112103510] [PMID: 25579574]
[2]
Hernandez JJ, Pryszlak M, Smith L, et al. Giving drugs a second chance: Overcoming regulatory and financial hurdles in repurposing approved drugs as cancer therapeutics. Front Oncol 2017; 7: 273-82.
[3]
Mehndiratta MM, Wadhai SA, Tyagi BK, et al. Drug repositioning. Int J Epilepsy 2016; 03(2): 91-4.
[http://dx.doi.org/10.1016/j.ijep.2016.09.002]
[4]
Wu Z, Wang Y, Chen L. Network-based drug repositioning. Mol Biosyst 2013; 9(6): 1268-81.
[http://dx.doi.org/10.1039/c3mb25382a] [PMID: 23493874]
[5]
Shim JS, Liu JO. Recent advances in drug repositioning for the discovery of new anticancer drugs. Int J Biol Sci 2014; 10(7): 654-63.
[http://dx.doi.org/10.7150/ijbs.9224] [PMID: 25013375]
[6]
Würth R, Thellung S, Bajetto A, Mazzanti M, Florio T, Barbieri F. Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds. Drug Discov Today 2016; 21(1): 190-9.
[http://dx.doi.org/10.1016/j.drudis.2015.09.017] [PMID: 26456577]
[7]
Xue H, Li J, Xie H, Wang Y. Review of drug repositioning approaches and resources. Int J Biol Sci 2018; 14(10): 1232-44.
[http://dx.doi.org/10.7150/ijbs.24612] [PMID: 30123072]
[8]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[9]
Oprea TI, Overington JP. Computational and practical aspects of drug repositioning. Assay Drug Dev Technol 2015; 13(6): 299-306.
[http://dx.doi.org/10.1089/adt.2015.29011.tiodrrr] [PMID: 26241209]
[10]
Sobhanzadeha Y, Omidib Y, Amanlou M, et al. Drug databases and their contributions to drug repurposing. Genomics 2019; 109: 254-62.
[PMID: 31226485]
[11]
Hurle MR, Yang L, Xie Q, Rajpal DK, Sanseau P, Agarwal P. Computational drug repositioning: from data to therapeutics. Clin Pharmacol Ther 2013; 93(4): 335-41.
[http://dx.doi.org/10.1038/clpt.2013.1] [PMID: 23443757]
[12]
Zhang P, Wang F, Hu J. Towards drug repositioning: a unified computational framework for integrating multiple aspects of drug similarity and disease similarity. AMIA Annu Symp Proc 2014; 2014: 1258-67.
[PMID: 25954437]
[13]
Kotelnikova E, Yuryev A, Mazo I, Daraselia N. Computational approaches for drug repositioning and combination therapy design. J Bioinform Comput Biol 2010; 8(3): 593-606.
[http://dx.doi.org/10.1142/S0219720010004732] [PMID: 20556864]
[14]
Nygren P, Fryknäs M, Agerup B, Larsson R. Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer. J Cancer Res Clin Oncol 2013; 139(12): 2133-40.
[http://dx.doi.org/10.1007/s00432-013-1539-5] [PMID: 24135855]
[15]
Pantziarka P, Bouche G, Meheus L, et al. The repurposing drugs in oncology (ReDO) project e-cancermedicalscience 2014; 8(442)
[16]
Aldea M, Craciun L, Tomuleasa C, et al. Repositioning metformin in cancer: genetics, drug targets, and new ways of delivery. Tumour Biol 2014; 35(6): 5101-10.
[http://dx.doi.org/10.1007/s13277-014-1676-8] [PMID: 24504677]
[17]
Pessetto ZY, Ma Y, Hirst JJ, von Mehren M, Weir SJ, Godwin AK. Drug repurposing identifies a synergistic combination therapy with imatinib mesylate for gastrointestinal stromal tumor. Mol Cancer Ther 2014; 13(10): 2276-87.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0043] [PMID: 25122069]
[18]
Chan MM, Chen R, Fong D. Targeting cancer stem cells with dietary phytochemical - Repositioned drug combinations. Cancer Lett 2018; 433: 53-64.
[http://dx.doi.org/10.1016/j.canlet.2018.06.034] [PMID: 29960048]
[19]
Clouser CL, Patterson SE, Mansky LM. Exploiting drug repositioning for discovery of a novel HIV combination therapy. J Virol 2010; 84(18): 9301-9.
[http://dx.doi.org/10.1128/JVI.01006-10] [PMID: 20610712]
[20]
Andrews KT, Fisher G, Skinner-Adams TS. Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist 2014; 4(2): 95-111.
[http://dx.doi.org/10.1016/j.ijpddr.2014.02.002] [PMID: 25057459]
[21]
Alberca LN, Sbaraglini ML, Balcazar D, et al. Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning. J Comput Aided Mol Des 2016; 30(4): 305-21.
[http://dx.doi.org/10.1007/s10822-016-9903-6] [PMID: 26891837]
[22]
Hassan M, Raza H, Abbasi MA, Moustafa AA, Seo SY. The exploration of novel Alzheimer’s therapeutic agents from the pool of FDA approved medicines using drug repositioning, enzyme inhibition and kinetic mechanism approaches. Biomed Pharmacother 2019; 109: 2513-26.
[http://dx.doi.org/10.1016/j.biopha.2018.11.115] [PMID: 30551512]
[23]
Murteira S, Millier A, Ghezaiel Z, et al. Drugreformulations and repositioning in the pharmaceutical industry and their impact on market access: regulatory implications. J Mark Access Health Policy 2014; 2(1): 22813.
[http://dx.doi.org/10.3402/jmahp.v2.22813]
[24]
Duran-Frigola M, Aloy P. Recycling side-effects into clinical markers for drug repositioning. Genome Med 2012; 4(1): 3-6.
[http://dx.doi.org/10.1186/gm302] [PMID: 22283977]
[25]
Murteira S, Ghezaiel Z, Karray S, Lamure M. Drug reformulations and repositioning in pharmaceutical industry and its impact on market access: reassessment of nomenclature. J Mark Access Health Policy 2013; 1(1): 1-16.
[http://dx.doi.org/10.3402/jmahp.v1i0.21131] [PMID: 27226826]
[26]
Smith R. Repositioned drugs: integrating intellectual property and regulatory strategies. Drug Discov Today Ther Strateg 2011; 8(3–4): 131-7.
[http://dx.doi.org/10.1016/j.ddstr.2011.06.008]
[27]
Moreira de Oliveira. Lang K. Drug repositioning: Concept, classification, methodology, and importance in rare/orphans and neglected diseases. J Appl Pharm Sci 2018; 8(8): 157-65.
[28]
Qureshi ZP, Seoane-Vazquez E, Rodriguez-Monguio R, Stevenson KB, Szeinbach SL. Market withdrawal of new molecular entities approved in the United States from 1980 to 2009. Pharmacoepidemiol Drug Saf 2011; 20(7): 772-7.
[http://dx.doi.org/10.1002/pds.2155] [PMID: 21574210]
[29]
Kativar S, Duvvuri S, Khan W, et al. Drug repurposing: A new era in drug discovery. Curr trends. Pharm Sci 2013; 1: 9-14.
[30]
Barnhill RL, McDougall AC. Thalidomide: use and possible mode of action in reactional lepromatous leprosy and in various other conditions. J Am Acad Dermatol 1982; 7(3): 317-23.
[http://dx.doi.org/10.1016/S0190-9622(82)70118-5] [PMID: 7130490]
[31]
Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 2006; 66(21): 10269-73.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1500] [PMID: 17062558]
[32]
Gerö D, Szoleczky P, Suzuki K, et al. Cell-based screening identifies paroxetine as an inhibitor of diabetic endothelial dysfunction. Diabetes 2013; 62(3): 953-64.
[http://dx.doi.org/10.2337/db12-0789] [PMID: 23223176]
[33]
Arico S, Pattingre S, Bauvy C, et al. Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem 2002; 277(31): 27613-21.
[http://dx.doi.org/10.1074/jbc.M201119200] [PMID: 12000750]
[34]
Howe LR, Subbaramaiah K, Patel J, et al. Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res 2002; 62(19): 5405-7.
[PMID: 12359744]
[35]
Galiè N, Ghofrani HA, Torbicki A, et al. Sildenafil use in pulmonary arterial hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353(20): 2148-57.
[http://dx.doi.org/10.1056/NEJMoa050010] [PMID: 16291984]
[36]
Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol 2004; 150(2): 186-94.
[http://dx.doi.org/10.1111/j.1365-2133.2004.05785.x] [PMID: 14996087]
[37]
Original Research-Phosphodiesterase inhibitor therapy for ED: Pharmacotherapy for erectile dysfunction. J Sex Med 2004; 1: 186-94.
[38]
Meinen S, Lin S, Ruegg MA. Angiotensin II type 1 receptor antagonists alleviate muscle pathology in the mouse model for laminin-α2-deficient congenital muscular dystrophy (MDC1A). Skelet Muscle 2012; 2(1): 18-24.
[http://dx.doi.org/10.1186/2044-5040-2-18] [PMID: 22943509]
[39]
Crunkhorn S. Metabolic disorders: Breaking the links between inflammation and diabetes. Nat Rev Drug Discov 2013; 12(4): 261.
[http://dx.doi.org/10.1038/nrd3988] [PMID: 23493085]
[40]
Sardana D, Zhu C, Zhang M, Gudivada RC, Yang L, Jegga AG. Drug repositioning for orphan diseases. Brief Bioinform 2011; 12(4): 346-56.
[http://dx.doi.org/10.1093/bib/bbr021] [PMID: 21504985]
[41]
Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 2004; 3(8): 673-83.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[42]
Jahchan NS, Dudley JT, Mazur PK, et al. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors. Cancer Discov 2013; 3(12): 1364-77.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0183] [PMID: 24078773]
[43]
Warrell RP Jr, Frankel SR, Miller WH Jr, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 1991; 324(20): 1385-93.
[http://dx.doi.org/10.1056/NEJM199105163242002] [PMID: 1850498]
[44]
Pillaiyar T, Meenakshisundaram S, Manickam M, Sankaranarayan M. A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery. Eur J Med Chem 2020; 195: 112275-82.
[45]
Ling L, Mengdi Hu M, Tao Wang Lu. Repositioning aspirin to treat lung and breast cancers and overcome acquired resistance to targeted therapy. Front Oncol 2019; 9: 1503-13.

Rights & Permissions Print Cite
Article Metrics
28
1
© 2024 Bentham Science Publishers | Privacy Policy