Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

Harnessing Drug Repurposing for Exploration of New Diseases: An Insight to Strategies and Case Studies

Author(s): Priti Jain*, Shreyans K. Jain and Munendra Jain

Volume 21, Issue 2, 2021

Published on: 19 June, 2020

Page: [111 - 132] Pages: 22

DOI: 10.2174/1566524020666200619125404

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Background: Traditional drug discovery is time consuming, costly, and risky process. Owing to the large investment, excessive attrition, and declined output, drug repurposing has become a blooming approach for the identification and development of new therapeutics. The method has gained momentum in the past few years and has resulted in many excellent discoveries. Industries are resurrecting the failed and shelved drugs to save time and cost. The process accounts for approximately 30% of the new US Food and Drug Administration approved drugs and vaccines in recent years.

Methods: A systematic literature search using appropriate keywords were made to identify articles discussing the different strategies being adopted for repurposing and various drugs that have been/are being repurposed.

Results: This review aims to describe the comprehensive data about the various strategies (Blinded search, computational approaches, and experimental approaches) used for the repurposing along with success case studies (treatment for orphan diseases, neglected tropical disease, neurodegenerative diseases, and drugs for pediatric population). It also inculcates an elaborated list of more than 100 drugs that have been repositioned, approaches adopted, and their present clinical status. We have also attempted to incorporate the different databases used for computational repurposing.

Conclusion: The data presented is proof that drug repurposing is a prolific approach circumventing the issues poised by conventional drug discovery approaches. It is a highly promising approach and when combined with sophisticated computational tools, it also carries high precision. The review would help researches in prioritizing the drugrepositioning method much needed to flourish the drug discovery research.

Keywords: Repurposing, approaches, rare diseases, cancer, neurodegenerative diseases, neglected tropical diseases, case studies, computational tools, and databases.

Next »
[1]
Iorio F, Rittman T, Ge H, Menden M, Saez-Rodriguez J. Transcriptional data: a new gateway to drug repositioning? Drug Discov Today 2013; 18(7-8): 350-7.
[http://dx.doi.org/10.1016/j.drudis.2012.07.014] [PMID: 22897878]
[2]
Priti J, Hemant RJ. Therapeutic advances in the treatment of Alzheimer’s disease: Present and future. Curr Drug Ther 2011; 6(3): 175-85.
[http://dx.doi.org/10.2174/157488511796391997]
[3]
Jin G, Wong STC. Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. Drug Discov Today 2014; 19(5): 637-44.
[http://dx.doi.org/10.1016/j.drudis.2013.11.005] [PMID: 24239728]
[4]
Dudley JT, Deshpande T, Butte AJ. Exploiting drug-disease relationships for computational drug repositioning. Brief Bioinform 2011; 12(4): 303-11.
[http://dx.doi.org/10.1093/bib/bbr013] [PMID: 21690101]
[5]
Bloom BE. Recent successes and future predictions on drug repurposing for rare diseases. Expert Opin Orphan Drugs 2016; 4(1): 1-4.
[http://dx.doi.org/10.1517/21678707.2016.1120664]
[6]
Durães F, Pinto M, Sousa E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals (Basel) 2018; 11(2)E44
[http://dx.doi.org/10.3390/ph11020044] [PMID: 29751602]
[7]
Sbaraglini ML, Vanrell MC, Bellera CL, et al. Neglected tropical protozoan diseases: Drug repositioning as a rational option. Curr Top Med Chem 2016; 16(19): 2201-22.
[http://dx.doi.org/10.2174/1568026616666160216154309] [PMID: 26881713]
[8]
Sbaraglini ML, Vanrell MC, Bellera CL, et al. Neglected tropical protozoan diseases: Drug repositioning as a rational option. Curr Top Med Chem 2016; 16(19): 2201-22.
[http://dx.doi.org/10.2174/1568026616666160216154309] [PMID: 26881713]
[9]
Burstein HJ. Off-label use of oncology drugs: too much, too little, or just right? J Natl Compr Canc Netw 2013; 11(5): 505-6.
[http://dx.doi.org/10.6004/jnccn.2013.0066] [PMID: 23667200]
[10]
Pfister DG. Off-label use of oncology drugs: the need for more data and then some. J Clin Oncol 2012; 30(6): 584-6.
[http://dx.doi.org/10.1200/JCO.2011.38.5567] [PMID: 22253470]
[11]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges, and recommendations. Nat Rev Drug Discov 2018.
[PMID: 30310233]
[12]
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]
[13]
Li YY, Jones SJ. Drug repositioning for personalized medicine. Genome Med 2012; 4(3): 27.
[http://dx.doi.org/10.1186/gm326] [PMID: 22494857]
[14]
Urquhart L. Market watch: Top drugs and companies by sales in 2017. Nat Rev Drug Discov 2018; 17(4): 232.
[http://dx.doi.org/10.1038/nrd.2018.42] [PMID: 29588516]
[15]
Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol 1998; 39(4 Pt 1): 578-89.
[http://dx.doi.org/10.1016/S0190-9622(98)70007-6] [PMID: 9777765]
[16]
Dudley JT, Sirota M, Shenoy M, et al. Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease. Sci Transl Med 2011; 3(96)96ra76
[http://dx.doi.org/10.1126/scitranslmed.3002648] [PMID: 21849664]
[17]
Auteri M, Zizzo MG, Serio R. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res 2015; 93: 11-21.
[http://dx.doi.org/10.1016/j.phrs.2014.12.001] [PMID: 25526825]
[18]
Iorio F, Bosotti R, Scacheri E, et al. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci USA 2010; 107(33): 14621-6.
[http://dx.doi.org/10.1073/pnas.1000138107] [PMID: 20679242]
[19]
Keiser MJ, Setola V, Irwin JJ, et al. Predicting new molecular targets for known drugs. Nature 2009; 462(7270): 175-81.
[http://dx.doi.org/10.1038/nature08506] [PMID: 19881490]
[20]
Campillos M, Kuhn M, Gavin AC, Jensen LJ, Bork P. Drug target identification using side-effect similarity. Science 2008; 321(5886): 263-6.
[http://dx.doi.org/10.1126/science.1158140] [PMID: 18621671]
[21]
Yang L, Agarwal P. Systematic drug repositioning based on clinical side-effects. PLoS One 2011; 6(12)e28025
[http://dx.doi.org/10.1371/journal.pone.0028025] [PMID: 22205936]
[22]
Grover MP, Ballouz S, Mohanasundaram KA, et al. Novel therapeutics for coronary artery disease from genome-wide association study data. BMC Med Genomics 2015; 8(2)(Suppl. 2): S1.
[http://dx.doi.org/10.1186/1755-8794-8-S2-S1] [PMID: 26044129]
[23]
Wu H, Huang J, Zhong Y, Huang Q. DrugSig: A resource for computational drug repositioning utilizing gene expression signatures. PLoS One 2017; 12(5)e0177743
[http://dx.doi.org/10.1371/journal.pone.0177743] [PMID: 28562632]
[24]
Wang ZY, Zhang HY. Rational drug repositioning by medical genetics. Nat Biotechnol 2013; 31(12): 1080-2.
[http://dx.doi.org/10.1038/nbt.2758] [PMID: 24316641]
[25]
Willyard C. New human gene tally reignites debate. Nature 2018; 558(7710): 354-5.
[http://dx.doi.org/10.1038/d41586-018-05462-w] [PMID: 29921859]
[26]
Lee BK, Tiong KH, Chang JK, et al. DeSigN: connecting gene expression with therapeutics for drug repurposing and development. BMC Genomics 2017; 18(Suppl. 1): 934.
[http://dx.doi.org/10.1186/s12864-016-3260-7] [PMID: 28198666]
[27]
Smith SB, Dampier W, Tozeren A, Brown JR, Magid-Slav M. Identification of common biological pathways and drug targets across multiple respiratory viruses based on human host gene expression analysis. PLoS One 2012; 7(3)e33174
[http://dx.doi.org/10.1371/journal.pone.0033174] [PMID: 22432004]
[28]
Greene CS, Voight BF. Pathway and network-based strategies to translate genetic discoveries into effective therapies. Hum Mol Genet 2016; 25(R2): R94-8.
[http://dx.doi.org/10.1093/hmg/ddw160] [PMID: 27340225]
[29]
Dakshanamurthy S, Issa NT, Assefnia S, et al. Predicting new indications for approved drugs using a proteochemometric method. J Med Chem 2012; 55(15): 6832-48.
[http://dx.doi.org/10.1021/jm300576q] [PMID: 22780961]
[30]
Sanseau P, Agarwal P, Barnes MR, et al. Use of genome-wide association studies for drug repositioning. Nat Biotechnol 2012; 30(4): 317-20.
[http://dx.doi.org/10.1038/nbt.2151] [PMID: 22491277]
[31]
Bartus RT, Bétourné A, Basile A, Peterson BL, Glass J, Boulis NM. β2-Adrenoceptor agonists as novel, safe and potentially effective therapies for Amyotrophic lateral sclerosis (ALS). Neurobiol Dis 2016; 85: 11-24.
[http://dx.doi.org/10.1016/j.nbd.2015.10.006] [PMID: 26459114]
[32]
Zi F, Zi H, Li Y, He J, Shi Q, Cai Z. Metformin and cancer: An existing drug for cancer prevention and therapy. Oncol Lett 2018; 15(1): 683-90.
[PMID: 29422962]
[33]
Herzig S, Raemy E, Montessuit S, et al. Identification and functional expression of the mitochondrial pyruvate carrier. Science 2012; 337(6090): 93-6.
[http://dx.doi.org/10.1126/science.1218530] [PMID: 22628554]
[34]
Ghosh A, Tyson T, George S, et al. Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson’s disease. Sci Transl Med 2016; 8(368)368ra174
[http://dx.doi.org/10.1126/scitranslmed.aag2210] [PMID: 27928028]
[35]
Miettinen TP, Björklund M. NQO2 is a reactive oxygen species generating off-target for acetaminophen. Mol Pharm 2014; 11(12): 4395-404.
[http://dx.doi.org/10.1021/mp5004866] [PMID: 25313982]
[36]
Alshareef A, Zhang HF, Huang YH, et al. The use of cellular thermal shift assay (CETSA) to study Crizotinib resistance in ALK-expressing human cancers. Sci Rep 2016; 6: 33710.
[http://dx.doi.org/10.1038/srep33710] [PMID: 27641368]
[37]
Brehmer D, Greff Z, Godl K, et al. Cellular targets of gefitinib. Cancer Res 2005; 65(2): 379-82.
[PMID: 15695376]
[38]
Blanke CD, Demetri GD, von Mehren M, et al. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 2008; 26(4): 620-5.
[http://dx.doi.org/10.1200/JCO.2007.13.4403] [PMID: 18235121]
[39]
Cohen P. Protein kinases--the major drug targets of the twenty-first century? Nat Rev Drug Discov 2002; 1(4): 309-15.
[http://dx.doi.org/10.1038/nrd773] [PMID: 12120282]
[40]
Hsieh YY, Chou CJ, Lo HL, Yang PM. Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer. Cell Death Discov 2016; 2: 16027.
[http://dx.doi.org/10.1038/cddiscovery.2016.27] [PMID: 27551518]
[41]
Xu M, Lee EM, Wen Z, et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med 2016; 22(10): 1101-7.
[http://dx.doi.org/10.1038/nm.4184] [PMID: 27571349]
[42]
Sun W, Weingarten RA, Xu M, et al. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria. Emerg Microbes Infect 2016; 5(11)e116
[http://dx.doi.org/10.1038/emi.2016.123] [PMID: 27826141]
[43]
Sawada R, Iwata H, Mizutani S, Yamanishi Y. Target-based drug repositioning using large-scale chemical-protein interactome data. J Chem Inf Model 2015; 55(12): 2717-30.
[http://dx.doi.org/10.1021/acs.jcim.5b00330] [PMID: 26580494]
[44]
Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther 2012; 342(1): 23-32.
[http://dx.doi.org/10.1124/jpet.112.192187] [PMID: 22431203]
[45]
Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther 2012; 342(1): 23-32.
[http://dx.doi.org/10.1124/jpet.112.192187] [PMID: 22431203]
[46]
Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther 2012; 342(1): 23-32.
[http://dx.doi.org/10.1124/jpet.112.192187] [PMID: 22431203]
[47]
Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther 2012; 342(1): 23-32.
[http://dx.doi.org/10.1124/jpet.112.192187] [PMID: 22431203]
[48]
Nosengo N. Can you teach old drugs new tricks? Nature 2016; 534(7607): 314-6.
[http://dx.doi.org/10.1038/534314a] [PMID: 27306171]
[49]
Thangamani S, Younis W, Seleem MN. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections. Sci Rep 2015; 5: 11596.
[http://dx.doi.org/10.1038/srep11596] [PMID: 26111644]
[50]
Vasaikar S, Bhatia P, Bhatia PG, Chu Yaiw K. Complementary approaches to existing target-based drug discovery for identifying novel drug targets. Biomedicines 2016; 4(4): 27.
[http://dx.doi.org/10.3390/biomedicines4040027] [PMID: 28536394]
[51]
Seliger C, Hau P. Drug repurposing of metabolic agents in malignant Glioma. Int J Mol Sci 2018; 19(9)E2768
[http://dx.doi.org/10.3390/ijms19092768] [PMID: 30223473]
[52]
Cousin MA, Ebbert JO, Wiinamaki AR, et al. Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment. PLoS One 2014; 9(3)e90467
[http://dx.doi.org/10.1371/journal.pone.0090467] [PMID: 24658307]
[53]
Gabapentin for chronic neuropathic pain in adults 6. Cochrane Database Syst Rev 2017; 6(6): 7938.
[54]
Fonseca VA, Handelsman Y, Staels B. Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidence. Diabetes Obes Metab 2010; 12(5): 384-92.
[http://dx.doi.org/10.1111/j.1463-1326.2009.01181.x] [PMID: 20415686]
[55]
Yella JK, Yaddanapudi S, Wang Y, Jegga AG. Changing trends in computational drug repositioning. Pharmaceuticals (Basel) 2018; 11(2)E57
[http://dx.doi.org/10.3390/ph11020057] [PMID: 29874824]
[56]
Blatt J, Corey SJ. Drug repurposing in pediatrics and pediatric hematology oncology. Drug Discov Today 2013; 18(1-2): 4-10.
[http://dx.doi.org/10.1016/j.drudis.2012.07.009] [PMID: 22835502]
[57]
Cheng F, Liu C, Jiang J, et al. Prediction of drug-target interactions and drug repositioning via network-based inference. PLOS Comput Biol 2012; 8(5)e1002503
[http://dx.doi.org/10.1371/journal.pcbi.1002503] [PMID: 22589709]
[58]
Chu CS, Tseng PT, Stubbs B, et al. Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis. Sci Rep 2018; 8(1): 5804.
[http://dx.doi.org/10.1038/s41598-018-24248-8] [PMID: 29643479]
[59]
Carroll CB, Wyse RKH. Simvastatin as a potential disease-modifying therapy for patients with Parkinson’s disease: Rationale for clinical trial, and current progress. J Parkinsons Dis 2017; 7(4): 545-68.
[http://dx.doi.org/10.3233/JPD-171203] [PMID: 29036837]
[60]
Liang Y, Besch-Williford C, Aebi JD, et al. Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071. Breast Cancer Res Treat 2014; 146(1): 51-62.
[http://dx.doi.org/10.1007/s10549-014-2996-5] [PMID: 24878988]
[61]
Wang T, Seah S, Loh X, et al. Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway. Oncotarget 2016; 7(3): 2532-44.
[http://dx.doi.org/10.18632/oncotarget.6304] [PMID: 26565813]
[62]
Tung RD. Deuterium medicinal chemistry comes of age. Future Med Chem 2016; 8(5): 491-4.
[http://dx.doi.org/10.4155/fmc-2016-0032] [PMID: 27079428]
[63]
Schmidt C. First deuterated drug approved. Nat Biotechnol 2017; 35(6): 493-4.
[http://dx.doi.org/10.1038/nbt0617-493] [PMID: 28591114]
[64]
Wu Z, Cheng F, Li J, Li W, Liu G, Tang Y. SDTNBI: an integrated network and chemoinformatics tool for systematic prediction of drug-target interactions and drug repositioning. Brief Bioinform 2017; 18(2): 333-47.
[PMID: 26944082]
[65]
Ferrari R, Lüscher TF. Reincarnated medicines: using out-dated drugs for novel indications. Eur Heart J 2016; 37(33): 2571-6.
[http://dx.doi.org/10.1093/eurheartj/ehw051] [PMID: 26957422]
[66]
Wulffraat NM. A safety evaluation of canakinumab for the treatment of systemic onset juvenile idiopathic arthritis. Expert Opin Drug Saf 2015; 14(12): 1961-7.
[http://dx.doi.org/10.1517/14740338.2016.1112377] [PMID: 26568054]
[68]
Ferreira LG, Andricopulo AD. Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective. Drug Discov Today 2016; 21(10): 1699-710.
[http://dx.doi.org/10.1016/j.drudis.2016.06.021] [PMID: 27365271]
[69]
Sun W, Sanderson PE, Zheng W. Drug combination therapy increases successful drug repositioning. Drug Discov Today 2016; 21(7): 1189-95.
[http://dx.doi.org/10.1016/j.drudis.2016.05.015] [PMID: 27240777]
[70]
Molina I, Salvador F, Sánchez-Montalvá A. The use of posaconazole against Chagas disease. Curr Opin Infect Dis 2015; 28(5): 397-407.
[http://dx.doi.org/10.1097/QCO.0000000000000192] [PMID: 26203852]
[71]
Monge-Maillo B, López-Vélez R. Miltefosine for visceral and cutaneous leishmaniasis: drug characteristics and evidence-based treatment recommendations. Clin Infect Dis 2015; 60(9): 1398-404.
[http://dx.doi.org/10.1093/cid/civ004] [PMID: 25601455]
[72]
Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 2012; 67(11): 2576-97.
[http://dx.doi.org/10.1093/jac/dks275] [PMID: 22833634]
[73]
Sanderson L, Yardley V, Croft SL. Activity of anti-cancer protein kinase inhibitors against Leishmania spp. J Antimicrob Chemother 2014; 69(7): 1888-91.
[http://dx.doi.org/10.1093/jac/dku069] [PMID: 24668412]
[74]
Miguel DC, Zauli-Nascimento RC, Yokoyama-Yasunaka JK, Katz S, Barbiéri CL, Uliana SR. Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections. J Antimicrob Chemother 2009; 63(2): 365-8.
[http://dx.doi.org/10.1093/jac/dkn509] [PMID: 19095684]
[75]
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]
[76]
Delavan B, Roberts R, Huang R, Bao W, Tong W, Liu Z. Computational drug repositioning for rare diseases in the era of precision medicine. Drug Discov Today 2018; 23(2): 382-94.
[http://dx.doi.org/10.1016/j.drudis.2017.10.009] [PMID: 29055182]
[77]
De Wachter E, Thomas M, Wanyama SS, Seneca S, Malfroot A. What can the CF registry tell us about rare CFTR-mutations? A Belgian study. Orphanet J Rare Dis 2017; 12(1): 142.
[http://dx.doi.org/10.1186/s13023-017-0694-1] [PMID: 28830496]
[78]
Condren ME, Bradshaw MD. Ivacaftor: a novel gene-based therapeutic approach for cystic fibrosis. J Pediatr Pharmacol Ther 2013; 18(1): 8-13.
[http://dx.doi.org/10.5863/1551-6776-18.1.8] [PMID: 23616732]
[79]
Lochmüller H, Torrent I, Farnell J, Le Cam Y, et al. IRDiRC Consortium Assembly. Policies and Guidelines to maximize impact. Eur J Hum Genet 2017; 25(12): 1293-302.
[http://dx.doi.org/10.1038/s41431-017-0008-z] [PMID: 29158551]
[80]
Marilynn L. 2018.
[81]
Kennedy L. Mifepristone and Cushing syndrome: A commentary. Endocr Pract 2015; 21(10): 1175-7.
[http://dx.doi.org/10.4158/EP15888.OR] [PMID: 26439001]
[82]
Liu R, Shi P, Nie Z, et al. Mifepristone suppresses basal triple-negative breast cancer stem cells by down-regulating KLF5 expression. Theranostics 2016; 6(4): 533-44.
[http://dx.doi.org/10.7150/thno.14315] [PMID: 26941846]
[84]
Platt FM. Emptying the stores: lysosomal diseases and therapeutic strategies. Nat Rev Drug Discov 2018; 17(2): 133-50.
[http://dx.doi.org/10.1038/nrd.2017.214] [PMID: 29147032]
[85]
Nacev BA, Grassi P, Dell A, Haslam SM, Liu JO. The antifungal drug itraconazole inhibits vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, trafficking, and signaling in endothelial cells. J Biol Chem 2011; 286(51): 44045-56.
[http://dx.doi.org/10.1074/jbc.M111.278754] [PMID: 22025615]
[86]
Jiao Y, Hannafon BN, Ding WQ. Disulfiram’s anticancer activity: Evidence and mechanisms. Anticancer Agents Med Chem 2016; 16(11): 1378-84.
[http://dx.doi.org/10.2174/1871520615666160504095040] [PMID: 27141876]
[87]
Pessetto ZY, Weir SJ, Sethi G, Broward MA, Godwin AK. Drug repurposing for gastrointestinal stromal tumor. Mol Cancer Ther 2013; 12(7): 1299-309.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0968] [PMID: 23657945]
[88]
Varbanov HP, Kuttler F, Banfi D, Turcatti G, Dyson PJ. Repositioning approved drugs for the treatment of problematic cancers using a screening approach. PLoS One 2017; 12(2)e0171052
[http://dx.doi.org/10.1371/journal.pone.0171052] [PMID: 28166232]
[89]
Dovrolis N, Kolios G, Spyrou G, Maroulakou I. Laying in silico pipelines for drug repositioning: a paradigm in ensemble analysis for neurodegenerative diseases. Drug Discov Today 2017; 22(5): 805-13.
[http://dx.doi.org/10.1016/j.drudis.2017.03.009] [PMID: 28363518]
[90]
Lempérière T. Encephale 2001; 27(4): 365-72. [Brief history of the development of valproate in bipolar disorders
[PMID: 11686059]
[91]
Appleby BS, Cummings JL. Discovering new treatments for Alzheimer’s disease by repurposing approved medications. Curr Top Med Chem 2013; 13(18): 2306-27.
[http://dx.doi.org/10.2174/15680266113136660162] [PMID: 24059463]
[92]
Heinrich M. Galanthamine from Galanthus and other Amaryllidaceae--chemistry and biology based on traditional use. Alkaloids Chem Biol 2010; 68: 157-65.
[http://dx.doi.org/10.1016/S1099-4831(10)06804-5] [PMID: 20334038]
[93]
Mucke HA. The case of galantamine: repurposing and late blooming of a cholinergic drug. Future Sci OA 2015; 1(4): FSO73.
[http://dx.doi.org/10.4155/fso.15.73] [PMID: 28031923]
[94]
Blakeley J, Grossman SA. Chemotherapy with cytotoxic and cytostatic agents in brain cancer. Handb Clin Neurol 2012; 104: 229-54.
[http://dx.doi.org/10.1016/B978-0-444-52138-5.00017-7] [PMID: 22230447]
[95]
Tousi B. The emerging role of bexarotene in the treatment of Alzheimer’s disease: current evidence. Neuropsychiatr Dis Treat 2015; 11: 311-5.
[http://dx.doi.org/10.2147/NDT.S61309] [PMID: 25709453]
[96]
Monacelli F, Cea M, Borghi R, Odetti P, Nencioni A. Do Cancer Drugs Counteract Neurodegeneration? Repurposing for Alzheimer’s Disease. J Alzheimers Dis 2017; 55(4): 1295-306.
[http://dx.doi.org/10.3233/JAD-160840] [PMID: 27834781]
[97]
Ibrahim NK. Zika virus: Epidemiology, current phobia and preparedness for upcoming mass gatherings, with examples from World Olympics and Pilgrimage. Pak J Med Sci 2016; 32(4): 1038-43.
[PMID: 27648063]
[98]
Devillers J. Repurposing drugs for use against Zika virus infection. SAR QSAR Environ Res 2018; 29(2): 103-15.
[http://dx.doi.org/10.1080/1062936X.2017.1411642] [PMID: 29299939]
[99]
Shiryaev SA, Mesci P, Pinto A, et al. Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis. Sci Rep 2017; 7(1): 15771.
[http://dx.doi.org/10.1038/s41598-017-15467-6] [PMID: 29150641]
[100]
Madenci E, Yilmaz K, Yilmaz M, Coskun Y. Alendronate treatment in osteogenesis imperfecta. J Clin Rheumatol 2006; 12(2): 53-6.
[http://dx.doi.org/10.1097/01.rhu.0000208490.22492.09] [PMID: 16601536]
[101]
Ward LM, Rauch F, Whyte MP, et al. Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Clin Endocrinol Metab 2011; 96(2): 355-64.
[http://dx.doi.org/10.1210/jc.2010-0636] [PMID: 21106710]
[102]
Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PA. Management of Kawasaki disease. Arch Dis Child 2014; 99(1): 74-83.
[http://dx.doi.org/10.1136/archdischild-2012-302841] [PMID: 24162006]
[103]
App EM, King M, Helfesrieder R, Köhler D, Matthys H. Acute and long-term amiloride inhalation in cystic fibrosis lung disease. A rational approach to cystic fibrosis therapy. Am Rev Respir Dis 1990; 141(3): 605-12.
[http://dx.doi.org/10.1164/ajrccm/141.3.605] [PMID: 2310093]
[104]
Lemonnier E, Degrez C, Phelep M, et al. A randomised controlled trial of bumetanide in the treatment of autism in children. Transl Psychiatry 2012; 2e202
[http://dx.doi.org/10.1038/tp.2012.124] [PMID: 23233021]
[105]
Hedlund-Treutiger I, Henter JI, Elinder G. Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol 2003; 25(2): 139-44.
[http://dx.doi.org/10.1097/00043426-200302000-00011] [PMID: 12571466]
[106]
Yang Y, Sun M, Cheng X, et al. Bleomycin A5 plus dexamethasone for control of growth in infantile parotid hemangiomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108(1): 62-9.
[http://dx.doi.org/10.1016/j.tripleo.2009.02.022] [PMID: 19451005]
[107]
Blatt J, Farag S, Corey SJ, et al. Expanding the scope of drug repurposing in pediatrics: the Children’s Pharmacy Collaborative. Drug Discov Today 2014; 19(11): 1696-8.
[http://dx.doi.org/10.1016/j.drudis.2014.08.003] [PMID: 25149597]
[108]
Rumore MM. Medication repurposing in pediatric patients: Teaching old drugs new tricks. J Pediatr Pharmacol Ther 2016; 21(1): 36-53.
[http://dx.doi.org/10.5863/1551-6776-21.1.36] [PMID: 26997928]
[109]
Fanti PA, Tosti A, Pileri S. Changes in Kaposi’s sarcoma induced by dapsone. Clin Exp Dermatol 1991; 16(6): 441-3.
[http://dx.doi.org/10.1111/j.1365-2230.1991.tb01231.x] [PMID: 1806319]
[110]
Brown AS, Patel CJ. A standard database for drug repositioning. Sci Data 2017; •••4170029
[http://dx.doi.org/10.1038/sdata.2017.29] [PMID: 28291243]
[111]
Moosavinasab S, Patterson J, Strouse R, et al. 2016.
[112]
Xu K, Coté TR. Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases. Brief Bioinform 2011; 12(4): 341-5.
[http://dx.doi.org/10.1093/bib/bbr006] [PMID: 21357612]
[113]
Martínez V, Navarro C, Cano C, Fajardo W, Blanco A. DrugNet: network-based drug-disease prioritization by integrating heterogeneous data. Artif Intell Med 2015; 63(1): 41-9.
[http://dx.doi.org/10.1016/j.artmed.2014.11.003] [PMID: 25704113]
[114]
Shameer K, Glicksberg BS, Hodos R, et al. Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning. Brief Bioinform 2018; 19(4): 656-78.
[http://dx.doi.org/10.1093/bib/bbw136] [PMID: 28200013]
[115]
Nagaraj AB, Wang QQ, Joseph P, et al. Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment. Oncogene 2018; 37(3): 403-14.
[http://dx.doi.org/10.1038/onc.2017.328] [PMID: 28967908]
[116]
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(5795): 1929-35.
[http://dx.doi.org/10.1126/science.1132939] [PMID: 17008526]
[117]
Subramanian A, Narayan R, Corsello SM, et al. 2017.
[118]
Huang H, Nguyen T, Ibrahim S, Shantharam S, Yue Z, Chen JY. DMAP: a connectivity map database to enable identification of novel drug repositioning candidates. BMC Bioinformatics 2015; 16(Suppl. 13): S4.
[http://dx.doi.org/10.1186/1471-2105-16-S13-S4] [PMID: 26423722]
[119]
Huang H, Wu X, Pandey R, et al. C2Maps: a network pharmacology database with comprehensive disease-gene-drug connectivity relationships. BMC Genomics 2012; 13(6)(Suppl. 6): S17.
[http://dx.doi.org/10.1186/1471-2164-13-S6-S17] [PMID: 23134618]
[120]
Neuwelt AJ, Wu YJ, Knap N, et al. Using acetaminophen’s toxicity mechanism to enhance cisplatin efficacy in hepatocarcinoma and hepatoblastoma cell lines. Neoplasia 2009; 11(10): 1003-11.
[http://dx.doi.org/10.1593/neo.09688] [PMID: 19794959]
[121]
Stachnik A, Yuen T, Iqbal J, et al. Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer. Proc Natl Acad Sci USA 2014; 111(50): 17995-8000.
[http://dx.doi.org/10.1073/pnas.1421422111] [PMID: 25453078]
[122]
Roy A, Chaguturu R. Holistic Drug TargetingInnovative Approaches in Drug Discovery. Boston: Academic Press 2017; pp. 65-88.
[http://dx.doi.org/10.1016/B978-0-12-801814-9.00003-9]
[123]
Lee H-M, Kim Y. Drug repurposing is a new opportunity for developing drugs against neuropsychiatric disorders. Schizophr Res Treatment 2016; 2016: 6378137-7.
[http://dx.doi.org/10.1155/2016/6378137] [PMID: 27073698]
[124]
Silveira CRA, MacKinley J, Coleman K, et al. Ambroxol as a novel disease-modifying treatment for Parkinson’s disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial. BMC Neurol 2019; 19(1): 20.
[http://dx.doi.org/10.1186/s12883-019-1252-3] [PMID: 30738426]
[125]
Vesterinen HM, Connick P, Irvine CMJ, et al. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis. PLoS One 2015; 10(4)e0117705
[http://dx.doi.org/10.1371/journal.pone.0117705] [PMID: 25856304]
[126]
Kirkegaard T, Gray J, Priestman DA, et al. Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses. Sci Transl Med 2016; 8(355)355ra118
[http://dx.doi.org/10.1126/scitranslmed.aad9823] [PMID: 27605553]
[127]
Benatar M, Wuu J, Andersen PM, et al. Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS. Neurology 2018; 90(7): e565-74.
[http://dx.doi.org/10.1212/WNL.0000000000004960] [PMID: 29367439]
[128]
Bernstein JE, Whitney DH, Soltani K. Inhibition of histamine-induced pruritus by topical tricyclic antidepressants. J Am Acad Dermatol 1981; 5(5): 582-5.
[http://dx.doi.org/10.1016/S0190-9622(81)70120-8] [PMID: 7298924]
[129]
Antman KH. Introduction: the history of arsenic trioxide in cancer therapy. Oncologist 2001; 6(Suppl. 2): 1-2.
[http://dx.doi.org/10.1634/theoncologist.6-suppl_2-1] [PMID: 11331433]
[130]
Patrignani P, Patrono C. Aspirin and Cancer. J Am Coll Cardiol 2016; 68(9): 967-76.
[http://dx.doi.org/10.1016/j.jacc.2016.05.083] [PMID: 27561771]
[131]
Seiler KP, George GA, Happ MP, et al. ChemBank: a small-molecule screening and cheminformatics resource database. Nucleic Acids Res 2008; 36(Database issue): D351-9.
[PMID: 17947324]
[132]
Lewis MG, DaFonseca S, Chomont N, et al. Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension. AIDS 2011; 25(11): 1347-56.
[http://dx.doi.org/10.1097/QAD.0b013e328347bd77] [PMID: 21505294]
[133]
Debnath A, Parsonage D, Andrade RM, et al. A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med 2012; 18(6): 956-60.
[http://dx.doi.org/10.1038/nm.2758] [PMID: 22610278]
[134]
Harbut MB, Vilchèze C, Luo X, et al. Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis. Proc Natl Acad Sci USA 2015; 112(14): 4453-8.
[http://dx.doi.org/10.1073/pnas.1504022112] [PMID: 25831516]
[135]
Park SH, Lee JH, Berek JS, Hu MC. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol 2014; 45(4): 1691-8.
[http://dx.doi.org/10.3892/ijo.2014.2579] [PMID: 25096914]
[136]
Rosenthal PJ. Azithromycin for Malaria? Am J Trop Med Hyg 2016; 95(1): 2-4.
[http://dx.doi.org/10.4269/ajtmh.16-0332] [PMID: 27215296]
[137]
Defronzo RA. Bromocriptine: a sympatholytic, d2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care 2011; 34(4): 789-94.
[http://dx.doi.org/10.2337/dc11-0064] [PMID: 21447659]
[138]
James BJ, Gales MA, Gales BJ. Bumetanide for Autism Spectrum Disorder in Children: A Review of Randomized Controlled Trials. Ann Pharmacother 2018; •••1060028018817304
[PMID: 30501497]
[139]
Leslie KS, Lachmann HJ, Bruning E, et al. Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations. Arch Dermatol 2006; 142(12): 1591-7.
[http://dx.doi.org/10.1001/archderm.142.12.1591] [PMID: 17178985]
[140]
Liu J, Lee J, Salazar Hernandez MA, Mazitschek R, Ozcan U. Treatment of obesity with celastrol. Cell 2015; 161(5): 999-1011.
[http://dx.doi.org/10.1016/j.cell.2015.05.011] [PMID: 26000480]
[141]
Tołoczko-Iwaniuk N, Dziemiańczyk-Pakieła D, Nowaszewska BK, Celińska-Janowicz K, Miltyk W. Celecoxib in cancer therapy and prevention - Review. Curr Drug Targets 2019; 20(3): 302-15.
[http://dx.doi.org/10.2174/1389450119666180803121737] [PMID: 30073924]
[142]
Massey TH, Robertson NP. Repurposing drugs to treat neurological diseases. J Neurol 2018; 265(2): 446-8.
[http://dx.doi.org/10.1007/s00415-018-8732-z] [PMID: 29322257]
[143]
Harlow DE, Honce JM, Miravalle AA. Remyelination therapy in multiple sclerosis. Front Neurol 2015; 6: 257-7.
[http://dx.doi.org/10.3389/fneur.2015.00257] [PMID: 26696956]
[144]
Deva S, Jameson M. Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer. Cochrane Database Syst Rev 2012; (8): CD007814
[http://dx.doi.org/10.1002/14651858.CD007814.pub2] [PMID: 22895966]
[145]
Nidorf SM, Thompson PL. Why colchicine should be considered for secondary prevention of atherosclerosis: An overview. Clin Ther 2019; 41(1): 41-8.
[http://dx.doi.org/10.1016/j.clinthera.2018.11.016] [PMID: 30591286]
[146]
Fonseca VA, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care 2008; 31(8): 1479-84.
[http://dx.doi.org/10.2337/dc08-0283] [PMID: 18458145]
[147]
Toppings NB, McMillan JM, Au PYB, Suchowersky O, Donovan LE. Wolfram Syndrome: A Case Report and Review of Clinical Manifestations, Genetics Pathophysiology, and Potential Therapies. Case Rep Endocrinol 2018; •••20189412676
[http://dx.doi.org/10.1155/2018/9412676] [PMID: 29850290]
[148]
Lindskov R, Reymann F. Dapsone in the treatment of cutaneous lupus erythematosus. Dermatologica 1986; 172(4): 214-7.
[http://dx.doi.org/10.1159/000249338] [PMID: 3519302]
[149]
Martin-Bastida A, Ward RJ, Newbould R, et al. Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson’s disease. Sci Rep 2017; 7(1): 1398.
[http://dx.doi.org/10.1038/s41598-017-01402-2] [PMID: 28469157]
[150]
Mullard A. 2015 FDA drug approvals. Nat Rev Drug Discov 2016; 15(2): 73-6.
[http://dx.doi.org/10.1038/nrd.2016.15] [PMID: 26837582]
[151]
Greenberger S, Bischoff J. Infantile hemangioma-mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med 2011; 1(1)a006460
[http://dx.doi.org/10.1101/cshperspect.a006460] [PMID: 22229118]
[152]
Purow B. Repurposing existing agents as adjunct therapies for glioblastoma. Neurooncol Pract 2016; 3(3): 154-63.
[http://dx.doi.org/10.1093/nop/npv041] [PMID: 31386097]
[153]
Trenti A, Boscaro C, Tedesco S, Cignarella A, Trevisi L, Bolego C. Effects of digitoxin on cell migration in ovarian cancer inflammatory microenvironment. Biochem Pharmacol 2018; 154: 414-23.
[http://dx.doi.org/10.1016/j.bcp.2018.06.008] [PMID: 29890142]
[154]
Valeriote F, Grates HE. Potentiation of nitrogen mustard cytotoxicity by disulfiram, diethyldithiocarbamic acid, and diethylamine in mice. Cancer Res 1989; 49(23): 6658-61.
[PMID: 2555050]
[155]
Aarsland D, Laake K, Larsen JP, Janvin C. Donepezil for cognitive impairment in Parkinson’s disease: a randomised controlled study. J Neurol Neurosurg Psychiatry 2002; 72(6): 708-12.
[http://dx.doi.org/10.1136/jnnp.72.6.708] [PMID: 12023410]
[156]
Brumatti G, Ma C, Lalaoui N, et al. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Sci Transl Med 2016; 8(339)339ra69
[http://dx.doi.org/10.1126/scitranslmed.aad3099] [PMID: 27194727]
[157]
Pazhayam NM, Chhibber-Goel J, Sharma A. New leads for drug repurposing against malaria. Drug Discov Today 2019; 24(1): 263-71.
[http://dx.doi.org/10.1016/j.drudis.2018.08.006] [PMID: 30099124]
[158]
Franz DN. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex. Biologics 2013; 7: 211-21.
[http://dx.doi.org/10.2147/BTT.S25095] [PMID: 24143074]
[159]
Song Y, Chen X, Wang L-Y, Gao W, Zhu M-J. Rho kinase inhibitor fasudil protects against β-amyloid-induced hippocampal neurodegeneration in rats. CNS Neurosci Ther 2013; 19(8): 603-10.
[http://dx.doi.org/10.1111/cns.12116] [PMID: 23638992]
[160]
Kanti V, Messenger A, Dobos G, et al. Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men - short version. J Eur Acad Dermatol Venereol 2018; 32(1): 11-22.
[http://dx.doi.org/10.1111/jdv.14624] [PMID: 29178529]
[161]
Aigner M, Treasure J, Kaye W, Kasper S. WFSBP Task Force On Eating Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry 2011; 12(6): 400-43.
[http://dx.doi.org/10.3109/15622975.2011.602720] [PMID: 21961502]
[162]
Serpell MG. Neuropathic pain study group. Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain 2002; 99(3): 557-66.
[http://dx.doi.org/10.1016/S0304-3959(02)00255-5] [PMID: 12406532]
[163]
Ghosh A, Pahan K. Gemfibrozil, a lipid-lowering drug, induces suppressor of cytokine signaling 3 in glial cells: implications for neurodegenerative disorders. J Biol Chem 2012; 287(32): 27189-203.
[http://dx.doi.org/10.1074/jbc.M112.346932] [PMID: 22685291]
[164]
Boepple PA, Mansfield MJ, Wierman ME, et al. Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty. Endocr Rev 1986; 7(1): 24-33.
[http://dx.doi.org/10.1210/edrv-7-1-24] [PMID: 2937629]
[165]
Plantone D, Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig 2018; 38(8): 653-71.
[http://dx.doi.org/10.1007/s40261-018-0656-y] [PMID: 29737455]
[166]
Stenvang J, Kümler I, Nygård SB, et al. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development. Front Oncol 2013; 3: 313.
[http://dx.doi.org/10.3389/fonc.2013.00313] [PMID: 24400218]
[167]
Zhang K, Hashimoto K. An update on ketamine and its two enantiomers as rapid-acting antidepressants. Expert Rev Neurother 2019; 19(1): 83-92.
[http://dx.doi.org/10.1080/14737175.2019.1554434] [PMID: 30513009]
[168]
Kim J, Tang JY, Gong R, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 2010; 17(4): 388-99.
[http://dx.doi.org/10.1016/j.ccr.2010.02.027] [PMID: 20385363]
[169]
Sartor O, Cutler GB Jr. Mifepristone: treatment of Cushing’s syndrome. Clin Obstet Gynecol 1996; 39(2): 506-10.
[http://dx.doi.org/10.1097/00003081-199606000-00024] [PMID: 8734015]
[170]
Zhang M, Luo H, Xi Z, Rogaeva E. Drug repositioning for diabetes based on ‘omics’ data mining. PLoS One 2015; 10(5)e0126082
[http://dx.doi.org/10.1371/journal.pone.0126082] [PMID: 25946000]
[171]
Ishida J, Konishi M, Ebner N, Springer J. Repurposing of approved cardiovascular drugs. J Transl Med 2016; 14(1): 269.
[http://dx.doi.org/10.1186/s12967-016-1031-5] [PMID: 27646033]
[172]
Tan SK, Jermakowicz A, Mookhtiar AK, Nemeroff CB, Schürer SC, Ayad NG. Drug repositioning in glioblastoma: A pathway perspective. Front Pharmacol 2018; 9(218): 218.
[http://dx.doi.org/10.3389/fphar.2018.00218] [PMID: 29615902]
[173]
Kozarek RA, Patterson DJ, Gelfand MD, Botoman VA, Ball TJ, Wilske KR. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 1989; 110(5): 353-6.
[http://dx.doi.org/10.7326/0003-4819-110-5-353] [PMID: 2492786]
[174]
Croft SL, Neal RA, Pendergast W, Chan JH. The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani. Biochem Pharmacol 1987; 36(16): 2633-6.
[http://dx.doi.org/10.1016/0006-2952(87)90543-0] [PMID: 3606662]
[175]
Siller SS, Broadie K. Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase. Dis Model Mech 2011; 4(5): 673-85.
[http://dx.doi.org/10.1242/dmm.008045] [PMID: 21669931]
[176]
Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG. MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. J Pharmacol Exp Ther 2012; 342(1): 15-22.
[http://dx.doi.org/10.1124/jpet.112.192096] [PMID: 22473614]
[177]
Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther 2006; 8(6): R182.
[http://dx.doi.org/10.1186/ar2093] [PMID: 17163990]
[178]
Taylor AM annd Sheperd L. The potential of nitisinone for the treatment of alkaptonuria. Expert Opin Orphan Drugs 2019; 7(10): 435-41.
[http://dx.doi.org/10.1080/21678707.2019.1664899]
[179]
Karuppagounder SS, Brahmachari S, Lee Y, Dawson VL, Dawson TM, Ko HS. The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson’s disease. Sci Rep 2014; 4: 4874.
[http://dx.doi.org/10.1038/srep04874] [PMID: 24786396]
[180]
Sukhatme V, Bouche G, Meheus L, Sukhatme VP, Pantziarka P. Repurposing Drugs in Oncology (ReDO)-nitroglycerin as an anti-cancer agent. Ecancermedicalscience 2015; 9: 568-8.
[http://dx.doi.org/10.3332/ecancer.2015.568] [PMID: 26435741]
[181]
Brum AM, van de Peppel J, van der Leije CS, et al. Connectivity Map-based discovery of parbendazole reveals targetable human osteogenic pathway. Proc Natl Acad Sci USA 2015; 112(41): 12711-6.
[http://dx.doi.org/10.1073/pnas.1501597112] [PMID: 26420877]
[182]
Muhsin M, Gricks C, Kirkpatrick P. Pemetrexed disodium. Nat Rev Drug Discov 2004; 3(10): 825-6.
[http://dx.doi.org/10.1038/nrd1528] [PMID: 15497247]
[183]
Camp AV. Penicillamine in the treatment of rheumatoid arthritis. Proc R Soc Med 1977; 70(2): 67-9.
[http://dx.doi.org/10.1177/003591577707000201] [PMID: 859814]
[184]
Mizuno T, Kinoshita S, Ito T, et al. Development of orthogonal linear separation analysis (OLSA) to decompose drug effects into basic components. Sci Rep 1824; 2019(9): 1-15.
[185]
Pantziarka P, Bouche G, Sukhatme V, Meheus L, Rooman I, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-Propranolol as an anti-cancer agent. Ecancermedicalscience 2016; 10: 680-0.
[http://dx.doi.org/10.3332/ecancer.2016.680] [PMID: 27899953]
[186]
Novac N. Challenges and opportunities of drug repositioning. Trends Pharmacol Sci 2013; 34(5): 267-72.
[http://dx.doi.org/10.1016/j.tips.2013.03.004] [PMID: 23582281]
[187]
Hadji P. The evolution of selective estrogen receptor modulators in osteoporosis therapy. Climacteric 2012; 15(6): 513-23.
[http://dx.doi.org/10.3109/13697137.2012.688079] [PMID: 22853318]
[188]
Virgili G, Parravano M, Menchini F, Evans JR. Anti-vascular endothelial growth factor for diabetic macular oedema. Cochrane Database Syst Rev 2014; (10): CD007419
[http://dx.doi.org/10.1002/14651858.CD007419.pub4] [PMID: 25342124]
[189]
Sun W, Zheng W, Simeonov A. Drug discovery and development for rare genetic disorders. Am J Med Genet A 2017; 173(9): 2307-22.
[http://dx.doi.org/10.1002/ajmg.a.38326] [PMID: 28731526]
[190]
Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 2014; 20(9): 1043-9.
[http://dx.doi.org/10.1038/nm.3645] [PMID: 25129481]
[191]
Kelly DP, Blatt J. Serendipitous drug repurposing through social media. Drug Discov Today 2019; 24(7): 1321-3.
[http://dx.doi.org/10.1016/j.drudis.2019.05.010] [PMID: 31102729]
[192]
Boyle AK, Rinaldi SF, Rossi AG, Saunders PTK, Norman JE. Repurposing simvastatin as a therapy for preterm labor: evidence from preclinical models. FASEB J 2019; 33(2): 2743-58.
[http://dx.doi.org/10.1096/fj.201801104R] [PMID: 30312114]
[193]
Roy A, Jana M, Kundu M, et al. HMG-CoA reductase inhibitors bind to pparalpha to upregulate neurotrophin expression in the brain and improve memory in mice. Cell Metab 2015; 22(2): 253-65.
[http://dx.doi.org/10.1016/j.cmet.2015.05.022] [PMID: 26118928]
[194]
Senniappan S, Alexandrescu S, Tatevian N, et al. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med 2014; 370(12): 1131-7.
[http://dx.doi.org/10.1056/NEJMoa1310967] [PMID: 24645945]
[195]
Činčárová L, Zdráhal Z, Fajkus J. New perspectives of valproic acid in clinical practice. Expert Opin Investig Drugs 2013; 22(12): 1535-47.
[http://dx.doi.org/10.1517/13543784.2013.853037] [PMID: 24160174]
[196]
Ahmed K, Shaw HV, Koval A, Katanaev VL. A second WNT for old drugs: Drug repositioning against wnt-dependent cancers. Cancers (Basel) 2016; 8(7)E66
[http://dx.doi.org/10.3390/cancers8070066] [PMID: 27429001]
[197]
Corriden R, Hollands A, Olson J, et al. Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide. Nat Commun 2015; 6: 8369.
[http://dx.doi.org/10.1038/ncomms9369] [PMID: 26458291]
[198]
Paik H, Chung A-Y, Park H-C, et al. Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records. Sci Rep 2015; 5: 8580.
[http://dx.doi.org/10.1038/srep08580] [PMID: 25739475]
[199]
Mohamed Ismail NA, Ibrahim M, Mohd Naim N, Mahdy ZA, Jamil MA, Mohd Razi ZR. Nifedipine versus terbutaline for tocolysis in external cephalic version. Int J Gynaecol Obstet 2008; 102(3): 263-6.
[http://dx.doi.org/10.1016/j.ijgo.2008.04.010] [PMID: 18554601]
[200]
Kozako T, Soeda S, Yoshimitsu M, et al. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. FEBS Open Bio 2016; 6(5): 442-60.
[http://dx.doi.org/10.1002/2211-5463.12055] [PMID: 27419050]
[201]
Boyer A, Pasquier E, Tomasini P, et al. Drug repurposing in malignant pleural mesothelioma: a breath of fresh air? Eur Respir Rev 2018; 27(147)170098
[http://dx.doi.org/10.1183/16000617.0098-2017] [PMID: 29540495]
[202]
D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91(9): 4082-5.
[http://dx.doi.org/10.1073/pnas.91.9.4082] [PMID: 7513432]
[203]
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]
[204]
Brodie SA, Brandes JC. Could valproic acid be an effective anticancer agent? The evidence so far. Expert Rev Anticancer Ther 2014; 14(10): 1097-100.
[http://dx.doi.org/10.1586/14737140.2014.940329] [PMID: 25017212]
[205]
Grothe DR, Scheckner B, Albano D. Treatment of pain syndromes with venlafaxine. Pharmacotherapy 2004; 24(5): 621-9.
[http://dx.doi.org/10.1592/phco.24.6.621.34748] [PMID: 15162896]
[206]
Ghanizadeh A, Freeman RD, Berk M. Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD: a systematic review of non-controlled and controlled trials. Rev Recent Clin Trials 2013; 8(1): 2-8.
[http://dx.doi.org/10.2174/1574887111308010002] [PMID: 23157376]
[207]
Hatzimouratidis K. Sildenafil in the treatment of erectile dysfunction: an overview of the clinical evidence. Clin Interv Aging 2006; 1(4): 403-14.
[http://dx.doi.org/10.2147/ciia.2006.1.4.403] [PMID: 18046917]
[208]
Guo F, Zhang H, McNair NN, Mead JR, Zhu G. The existing drug vorinostat as a new lead against cryptosporidiosis by targeting the parasite histone deacetylases. J Infect Dis 2018; 217(7): 1110-7.
[http://dx.doi.org/10.1093/infdis/jix689] [PMID: 29300993]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy