Drug Repositioning Identifies Six Drug Candidates for Systemic Autoimmune Diseases by Integrative Analyses of Transcriptomes from Scleroderma, Systemic Lupus Erythematosus, and Sjogren's Syndrome

dc.authorscopusid 57210286566
dc.authorscopusid 56417822000
dc.contributor.author Oktem, Elif Kubat
dc.contributor.author Yazar, Metin
dc.date.accessioned 2024-05-25T11:26:27Z
dc.date.available 2024-05-25T11:26:27Z
dc.date.issued 2022
dc.department Okan University en_US
dc.department-temp [Oktem, Elif Kubat] Istanbul Medeniyet Univ, Fac Engn & Nat Sci, Dept Mol Biol & Genet, Istanbul, Turkey; [Yazar, Metin] Istanbul Okan Univ, Fac Engn & Nat Sci, Dept Genet & Bioengn, Istanbul, Turkey; [Yazar, Metin] Marmara Univ, Fac Engn, Dept Bioengn, Istanbul, Turkey en_US
dc.description.abstract The mechanisms of systemic autoimmune diseases (ADs) are still not clearly understood. Understanding the etiology of systemic ADs and identifying new therapeutic targets require a systems science approach. Using publicly available transcriptome data and bioinformatic analysis, we investigated the differential gene expression profiles of patients with scleroderma, systemic lupus erythematosus, and Sjogren's syndrome. Of these common differentially expressed gene signatures, 208 were regulated in the same direction (either upregulated or downregulated in all datasets) and used for drug repositioning. Six small molecule drug candidates (KU-0063794, YM-155 [sepantronium bromide], MST-312 [telomerase inhibitor IX], PLX-4720, ZM 336372, and 528116.cdx [PIK-75]) were discovered by drug repositioning as potential therapeutics for systemic ADs. The Search Tool for Chemical Interactions was used to find the anticipated target genes of the repositioned molecules. The PI3K/AKT pathway topped the list of common enriched pathways with the most anticipated target genes of the six repositioned small molecules. We also report here the molecular docking findings on the binding affinity between the repositioned drug candidates and genes from the protein-protein interaction network modules of anticipated target genes. Taken together, this study provides new insights and opens up new possibilities on both pathogenesis and treatment of systemic ADs through drug repositioning. en_US
dc.identifier.citationcount 2
dc.identifier.doi 10.1089/omi.2022.0138
dc.identifier.endpage 693 en_US
dc.identifier.issn 1536-2310
dc.identifier.issn 1557-8100
dc.identifier.issue 12 en_US
dc.identifier.pmid 36378860
dc.identifier.scopus 2-s2.0-85144094339
dc.identifier.scopusquality Q3
dc.identifier.startpage 683 en_US
dc.identifier.uri https://doi.org/10.1089/omi.2022.0138
dc.identifier.uri https://hdl.handle.net/20.500.14517/958
dc.identifier.volume 26 en_US
dc.identifier.wos WOS:000885569400001
dc.identifier.wosquality Q2
dc.institutionauthor Yazar M.
dc.language.iso en
dc.publisher Mary Ann Liebert, inc en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/closedAccess en_US
dc.scopus.citedbyCount 2
dc.subject bioinformatics en_US
dc.subject drug repositioning en_US
dc.subject systems biology en_US
dc.subject scleroderma en_US
dc.subject systemic lupus erythematosus en_US
dc.subject Sjogren's syndrome en_US
dc.title Drug Repositioning Identifies Six Drug Candidates for Systemic Autoimmune Diseases by Integrative Analyses of Transcriptomes from Scleroderma, Systemic Lupus Erythematosus, and Sjogren's Syndrome en_US
dc.type Article en_US
dc.wos.citedbyCount 2

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