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25cm; line-height: 120%; }a:link { }Summaryon Drug RepositioningZirsanglal TripuraTrainee, SCIS , JNUDated: 29/01/2018Drug Repositioning or drug repurposing is one of the most effectivemethod of drug discovery, its basic principle is finding a new targetfor existing drug, this practice is commonly practiced byphermacutical companies during the drug discovery process in order toadjust or expand the application line of the activemolecule1.History of Drug repositioning came from long back beforethe systamatic effort came to existance (e.g 2006) coz during thepast discovery of new uses of old drugs is mostly throughserendipity2. Here in Table 1 shows the new indiacations of drugsand the year of approval.Table 1.Listof repositioned compounds updated and supplemented with informationon compound approval Drug Original indication New indication Year Amphetamine Stimulant Hyperkinesis in Children(attention deficit hyperactivity disorder, ADHD) 1943 Allopurinol Tumor lysis syndrome Gout 1967 Zidovudine Cancer HIV/AIDS 1985 Minoxidil Hypertension Alopecia 1988 Bupropion Depression Smoking cessation 1997 Sibutramine Deprassion Obesity 1997 Finasteride Benign prostatic hyperplasia Alopecia 1997 Methotrexate Cancer Rheumatoid arthritis 1999 Fluoxetine Depression Premenstrual dysphoric disorder 2000 Atomoxetine Parkinson’s disease ADHD 2002 Thalidormide Morning Sickness Multiple myeloma 2003 Cymbalta Depression Diabetic peripheral neuropathy 2004 Topiramate Epilepsay Migraine 2004 Paclitaxel Cancer Restenosis 2004 Drug repositioning became a promising, fast, and cost effectivemethod that can overcome traditional de novo drug discovery anddevelopment challenges of targeting neuropsychiatric3 and otherdesiseases like the neglected tropical diseases. Drug repurposing aregrowing significantly growing as for non–profit organizations, inassociation with academia and pharmaceutical companies, are running screening campaigns for the identification of new repositioningcandidates4. One of the main reasons for the sucess of drugrepositioning is because a repositioned drug does not require longterm duration (i.

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e 6-9 years) for the development of new drugs, butinstead goes directly to preclinical testing and clinical trials,thus reducing risk and costs5. One of the well-known examples issildenafil citrate (brand name: Viagra), which was repositioned froma common hypertension drug to a therapy for erectile dysfunction 6.General Strategies applied for Drug repositioningGenome: In this type of drug repurposing stratagy cellularfunction at genome level is understood and target is choosed viagenomic and transcriptomic data for a diverse set of disease. Some ofthe method use are CMAP7 , Guilt by Asociation, Gene Silencing,Genome Wide Association studies(GWAS) CMAP aims to construct adetailed map for functional associations among diseases, geneticperturbations and drug actions. By integrating with other functionalgenomics databases e.

g. NCBI Gene Expression Omnibus (GEO), areextensively explored in drug repositioning studies. Guilt by association finds for drugs that has similartranscriptional responses which estimates that they could have samemode of action (MoA)8 Gene Silencing , some non coding sequences act as gene silencing eg.MicroRNA or miRNA act as RNA silencing and post transcriptionalregulation of gene expresion, thus becoming a theraputic target fordrug repositioning9. Agenome-wide association study (GWA study, or GWAS),also known as whole genome association study (WGA study,or WGAS), is an study of a genome-wide set of genetic varientsin different individuals to find out any variant is associated with atrait it typically focus on associations between single nucleotidepolymorphisam (SNPs) and traits like major human & otherorganisam diseases10.Phenome:Its a study of pheotypicrelationship of the disease related associations which has became aemarging area of drug repositioning work.

Some organisation likePheWAS(Phenome wide Association Studies) recently came up and becamepopular with their approach to identify genetic associations withhuman diseases.11Drug Chemical Structure:The chemical structure ofthe drug can also be an important point towards reposition of drug ,the avaibility of huge ammount of of biochemical data in opensourcedatabases gives useful information of drug repositioning. Thekey reason behind this concept is molecules with similar chemicalstructure offen affect proteins and biological systems in the sameway.For example, Swamidass et al. 12 proposed to use chemical structureto deduce which targets modulate disease-relevant phenotype. Knowingwhich targets modulate disease-relevant phenotypes is a signal thatcan indicate what other drugs might work to treat the disease.Drug Combination: Referances:-1.Croset,S.

(2014). Drugrepositioning and indication discovery using description logics(Doctoral dissertation, University of Cambridge).2.Bolgar B,Arany A, Temesi G.

et al., Drug repositioning for treatment ofmovement disorders: from serendipity to rational discoverystrategies. Curr Top Med Chem 2013;13(18): 2337–63.3. Lee,Hyeong-Min, and Yuna Kim. “Drug repurposing is a new opportunityfor developing drugs against neuropsychiatric disorders.”Schizophreniaresearch and treatment2016 (2016).4.

Ferreira,Leonardo G., and Adriano D. Andricopulo. “Drug repositioningapproaches to parasitic diseases: a medicinal chemistry perspective.”Drugdiscovery today21.10 (2016): 1699-1710.5.

Ashburn,T.T. and Thor, K.B. (2004) Drug repositioning: identifying anddeveloping newuses for existing drugs.

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3, 673–6836.Novac,N. (2013) Challenges and opportunities of drug repositioning. TrendsPharmacol.

Sci. 34, 267–2727.Lamb,Justin, et al. “The Connectivity Map: using gene-expressionsignatures to connect small molecules, genes, and disease.

“science313.5795 (2006): 1929-1935.8.IorioF, Rittman T, Ge H, et al. Transcriptional data: a new gateway todrug repositioning? Drug DiscovToday 2013; 18(7–8):350–7.9.

Xing,Zhiwei, et al. “MicroRNAs and anticancer drugs.” ActaBiochim Biophys Sin46.3 (2014): 233-239.10.

SanseauP, Agarwal P, Barnes MR, et al. Use of genome-wide associationstudies for drug repositioning. Nat Biotechnol2012;30(4):317–20.11.HebbringSJ. The challenges, advantages and future of phenome-wide associationstudies. Immunology 2014;141(2):157–65.

12.SwamidassSJ. Mining small-molecule screens to repurpose drugs. Brief Bioinform2011; 12(4) :327–35.