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Original Articles

Drug repurposing for rheumatoid arthritis: Identification of new drug candidates via bioinformatics and text mining analysis

ORCID Icon, , ORCID Icon & ORCID Icon
Pages 147-156 | Received 31 Oct 2021, Accepted 07 Jan 2022, Published online: 20 Jan 2022

References

  • Banchereau R, Cepika A-M, Banchereau J, et al. Understanding human autoimmunity and autoinflammation through transcriptomics. Annu Rev Immunol. 2017;35:337–370.
  • Liu Y, Yin H, Zhao M, et al. TLR2 and TLR4 in autoimmune diseases: a comprehensive review. Clin Rev Allergy Immunol. 2014;47(2):136–147.
  • Krishna V, Yin X, Song Q, et al. Integration of the transcriptome and genome-wide landscape of BRD2 and BRD4 binding motifs identifies key superenhancer genes and reveals the mechanism of bet inhibitor action in rheumatoid arthritis synovial fibroblasts. J Immunol. 2021;206(2):422–431.
  • Cohn M. Autoimmunity: Rationalizing possible pathways from initiation to disease. J Theor Biol. 2015;375:40–51.
  • Udalova IA, Mantovani A, Feldmann M. Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol. 2016;12(8):472–485.
  • Song X, Lin Q. Genomics, transcriptomics and proteomics to elucidate the pathogenesis of rheumatoid arthritis. Rheumatol Int. 2017;37(8):1257–1265.
  • Frank-Bertoncelj M, Klein K, Gay S. Interplay between genetic and epigenetic mechanisms in rheumatoid arthritis. Epigenomics. 2017;9(4):493–504.
  • Craddock N, Hurles ME, Cardin N, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. 2010;464(7289):713–720.
  • Eyre S, Bowes J, Diogo D, Wellcome Trust Case Control Consortium, et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012;44(12):1336–1340.,
  • Ai R, Hammaker D, Boyle DL, et al. Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes. Nat Commun. 2016;7:11849
  • Teixeira VH, Olaso R, Martin-Magniette M-L, et al. Transcriptome analysis describing new immunity and defense genes in peripheral blood mononuclear cells of rheumatoid arthritis patients. PloS One. 2009;4(8):e6803. Aug
  • Pauley KM, Cha S, Chan EKL. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 2009;32(3-4):189–194.
  • Chen J-Q, Papp G, Szodoray P, et al. The role of microRNAs in the pathogenesis of autoimmune diseases. Autoimmun Rev. 2016;15(12):1171–1180.
  • Paul SM, Mytelka DS, Dunwiddie CT, et al. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov. 2010;9(3):203–214.
  • Nosengo N. Can you teach old drugs new tricks? Nature. England. 2016;534(7607):314–316.
  • Gupta SC, Sung B, Prasad S, et al. Cancer drug discovery by repurposing: teaching new tricks to old dogs. Trends Pharmacol Sci. 2013;34(9):508–517.
  • Demirel A, Kirnap M. Traditional and up-to-date treatment in rheumatoid arthtiris. Saglık bilimleri dergisi. (Journal of Health Sciences). 2010;19(1):74–84.
  • Comertpay B, Gov E. Identification of key biomolecules in rheumatoid arthritis through the reconstruction of comprehensive disease-specific biological networks. Autoimmunity. 2020; 53(3):156–166.
  • Auwul MR, Rahman MR, Gov E, et al. Bioinformatics and machine learning approach identifies potential drug targets and pathways in COVID-19. Brief Bioinform. 2021;22(5)
  • Erceylan ÖF, Savaş A, Göv E. Targeting the tumor stroma: integrative analysis reveal GATA2 and TORYAIP1 as novel prognostic targets in breast and ovarian cancer. Turk J Biol. 2021;45(2):127–137.
  • Comertpay B, Gulfidan G, Arga KY, et al. Cancer stem cell transcriptome profiling reveals seed genes of tumorigenesis: New avenues for cancer precision medicine. OMICS. 2021;25(6):372–388.
  • Gulfidan G, Beklen H, Sinha I, et al. Differential protein interactome in esophageal squamous cell carcinoma offers novel systems biomarker candidates with high diagnostic and prognostic performance. OMICS. 2021;25(8):495–512.
  • Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res. 2013;41(Database issue):D991–5.
  • Woetzel D, Huber R, Kupfer P, et al. Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation. Arthritis Res Ther. 2014;16(2):R84
  • Broeren MGA, de Vries M, Bennink MB, Arntz OJ, et al. Disease-Regulated gene therapy with anti-Inflammatory interleukin-10 under the control of the CXCL10 promoter for the treatment of rheumatoid Arthritis. Hum Gene Ther. 2016;27(3):244–254.
  • Ungethuem U, Haeupl T, Witt H, et al. Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol Genomics. 2010;42A(4):267–282.
  • Yarilina A, Park-Min K-H, Antoniv T, et al. TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes. Nat Immunol. 2008;9(4):378–387.
  • Kang K, Park SH, Chen J, et al. Interferon-γ represses M2 gene expression in human macrophages by disassembling enhancers bound by the transcription factor MAF. Immunity. 2017;47(2):235–250.e4.
  • Tasaki S, Suzuki K, Kassai Y, et al. Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission. Nat Commun. 2018;9(1):2755
  • Bolstad BM, Irizarry RA, Åstrand M, et al. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19(2):185–193.
  • Smyth GK. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3(1):1–25.
  • Kamburov A, Pentchev K, Galicka H, et al. ConsensusPathDB: toward a more complete picture of cell biology. Nucleic Acids Res. 2011;39(Database issue):D712–7.
  • Oughtred R, Rust J, Chang C, et al. The BioGRID database: a comprehensive biomedical resource of curated protein, genetic, and chemical interactions. Protein Sci. 2021;30(1):187–200.
  • Smoot ME, Ono K, Ruscheinski J, et al. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2011;27(3):431–432.
  • Bovolenta LA, Acencio ML, Lemke N. HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions. BMC Genomics. 2012;13:405.
  • Gov E, Arga KY. Interactive cooperation and hierarchical operation of microRNA and transcription factor crosstalk in human transcriptional regulatory network. IET Syst Biol. 2016;10(6):219–228.
  • Chou C-H, Chang N-W, Shrestha S, et al. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 2016;44(D1):D239–47.
  • Cotto KC, Wagner AH, Feng Y-Y, et al. DGIdb 3.0: a redesign and expansion of the drug-gene interaction database. Nucleic Acids Res. 2018;46(D1):D1068–73.
  • urllib3 1.26.7 [Internet]. Available from: https://pypi.org/project/urllib3/.
  • Canese K, Weis S PubMed : the bibliographic database. In: The NCBI handbook. 2013. p. 1–12.
  • Cock PJA, Antao T, Chang JT, et al. Biopython: freely available python tools for computational molecular biology and bioinformatics. Bioinformatics. 2009;25(11):1422–1423. Jun
  • Bardou P, Mariette J, Escudié F, et al. SOFTWARE open access jvenn: an interactive venn diagram viewer. BMC Bioinformatics. [Internet]. 2014;15(293):293–297. Available from: http://www.biomedcentral.com/1471-2105/15/293
  • Zhao Z, Ukidve A, Kim J, et al. Targeting strategies for Tissue-Specific drug delivery. Cell. 2020;181(1):151–167.
  • Corticosteroids [Internet]. LiverTox: Clinical and research information on Drug-Induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. [cited 2021 Oct 11]. Available from: https://pubmed.ncbi.nlm.nih.gov/31643719/
  • Harris EDJ, Emkey RD, Nichols JE, et al. Low dose prednisone therapy in rheumatoid arthritis: a double blind study. J Rheumatol. 1983;10(5):713–721. Oct
  • van Everdingen AA, Jacobs JWG, Siewertsz Van Reesema DR, et al. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002;136(1):1–12.
  • Pincus T, Marcum SB, Callahan LF. Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol. 1992;19(12):1885–1894.
  • Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256–1269.
  • CALQUENCE® (acalabrutinib) capsules, for oral use Initial U.S. Approval: 2017. [Internet]. AstraZeneca Pharmaceuticals LP; 4523127 [cited 2021 Oct 10]. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210259s006s007lbl.pdf.
  • ACP-196 Versus Placebo in Subjects With Rheumatoid Arthritis on Background MethotrexateNo Title [Internet]. U.S. National Library of Medicine ClinicalTrials.gov. [cited 2021. Oct 10]. Available at: https://clinicaltrials.gov/ct2/show/study/NCT02387762.
  • Forsythe P, Paterson S. Ciclosporin 10 years on: indications and efficacy. The Veterinary Record. 2014;174(S2):13–21. Mar
  • Johns KR, Littlejohn GO. The safety and efficacy of cyclosporine (neoral) in rheumatoid arthritis. The. J Rheumatol. 1999;26(10):2110–2113.
  • Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. The. N Engl J Med. 1994;330(26):1841–1845.
  • Kappers-Klunne MC, van’t Veer MB. Cyclosporin a for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001;114(1):121–125.
  • Lee SH, Chung H, Yu HG. Clinical outcomes of cyclosporine treatment for noninfectious uveitis. Korean J Ophthalmol. 2012;26(1):21–25.
  • Yang TH, Wu TH, Chang YL, et al. Cyclosporine for the treatment of lupus nephritis in patients with systemic lupus erythematosus. CN. 2018;89(4):277–285.
  • Tyner JW, Bumm TG, Deininger J, Wood L, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood. 2010;115(25):5232–5240. Jun
  • Gupta V, Mesa RA, Deininger MWN, et al. A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis. Haematologica. 2017;102(1):94–102. Jan
  • Tymoszuk P, Petzer V, Asshoff M, et al. Momelotinib, a janus kinase 1/2 and activin receptor 1 inhibitor, ameliorates joint inflammation, systemic Th17 differentiation and Arthritis-Linked anemia in Pre-Clinical autoimmune RA. Ann Rheum Dis. 2020;79(Suppl 1):940.1–940. [Internet]. – Available from: http://ard.bmj.com/content/79/Suppl_1/940.1.abstract
  • Berglöf A, Hamasy A, Meinke S, et al. Targets for ibrutinib beyond B cell malignancies. Scand J Immunol. 2015;82(3):208–217. Sep
  • Papanota A-M, Ntanasis-Stathopoulos I, Kastritis E, et al. Evaluating ibrutinib in the treatment of symptomatic Waldenstrom's macroglobulinemia. J Blood Med. 2019;10:291–300.
  • Miklos D, Cutler CS, Arora M, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130(21):2243–2250. Nov
  • Kim S, Chen J, Cheng T, et al. PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res. 2021;49(D1):D1388–D1395.
  • Kim DS, Kwon J-E, Lee SH, et al. Attenuation of rheumatoid inflammation by sodium butyrate through reciprocal targeting of HDAC2 in osteoclasts and HDAC8 in T cells. Front Immunol. 2018;9:1525.
  • Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–82.
  • Sharma S, Mulik S, Kumar N, et al. An anti-inflammatory role of VEGFR2/src kinase inhibitor in herpes simplex virus 1-induced immunopathology. J Virol. 2011;85(12):5995–6007. Jun
  • Mousa SA, Mousa SS. Current status of vascular endothelial growth factor inhibition in age-related macular degeneration. BioDrugs : Clin Immunotherapeut BiopharmaceuticalsGene Therapy. 2010;24(3):183–194.
  • Gijsen M, King P, Perera T, et al. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer. PLoS Biol. 2010;8(12):e1000563
  • Gadina M, Schwartz DM, O'Shea JJ. Decernotinib: a Next-Generation Jakinib. Arthritis Rheumatol. 2016;68(1):31–34.
  • Genovese MC, van Vollenhoven RF, Pacheco-Tena C, et al. VX-509 (decernotinib), an oral selective JAK-3 inhibitor, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis & Rheumatology (Hoboken, NJ. 2016;68(1):46–55.
  • Fleischmann RM, Damjanov NS, Kivitz AJ, et al. A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients with active rheumatoid arthritis. Arthr Rheumatol. 2015;67(2):334–343. ). Feb
  • Genovese MC, Yang F, Østergaard M, et al. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings. Ann Rheum Dis. 2016;75(11):1979–1983. Nov
  • Mogul A, Corsi K, McAuliffe L. Baricitinib: the second FDA-Approved JAK inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother. 2019;53(9):947–953. Sep
  • Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506–517. Mar
  • Schiff M, Takeuchi T, Fleischmann R, et al. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther. 2017;19(1):208
  • Keystone EC, Taylor PC, Drescher E, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2015;74(2):333–340.
  • Itacitinib [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004. PubChem Compound Summary for CID 53380437. [cited 2021 Oct 10]. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Itacitinib.
  • A Study Exploring the Safety, Tolerability, and Efficacy of a 28 Day Course Followed by an Additional 56 Day Course of Itacitinib in Subjects With Active Rheumatoid Arthritis [Internet]. U.S. National Library of Medicine ClinicalTrials.gov. 2012. [cited 2021 Oct 10]. Available at: https://clinicaltrials.gov/ct2/show/NCT01626573.
  • McMullin MF, Harrison CN, Niederwieser D, et al. The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis. Exp Hematol Oncol. 2015;4:26.
  • Weinacht KG, Charbonnier L-M, Alroqi F, et al. Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J Allergy Clin Immunol. 2017; May139(5):1629–1640.e2.
  • Higgins E, Al Shehri T, McAleer MA, et al. Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation. J Allergy Clin Immunol. 2015;135(2):551–553. Vol.
  • A Study Exploring the Safety, Tolerability and Efficacy of a 4 Week Course of INCB018424 in Subjects With Active Rheumatoid Arthritis [Internet]. U.S. National Library of Medicine ClinicalTrials.gov. 2015. [cited 2021 Oct 10]. Available at: https://clinicaltrials.gov/ct2/show/NCT00550043.
  • Cheon JH, Kim JY, Lee B-M, et al. P-gp inhibition by XL019, a JAK2 inhibitor, increases apoptosis of vincristine-treated resistant KBV20C cells with increased p21 and pH2AX Expression. Anticancer Res. 2017;37(12):6761–6769.
  • Tseng S, Pak G, Washenik K, et al. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. 1996;35(6):969–979.
  • Richardson P, Hideshima T, Anderson K. Thalidomide: emerging role in cancer medicine. Annu Rev Med. 2002;53:629–657.
  • Gutiérrez-Rodríguez O. Thalidomide. A promising new treatment for rheumatoid arthritis. Arthritis Rheum. 1984;27(10):1118–1121.
  • Gutiérrez-Rodríguez O, Starusta-Bacal P, Gutiérrez-Montes O. Treatment of refractory rheumatoid arthritis–the thalidomide experience. J Rheumatol. 1989; 16(2):158–163.
  • Lehman TJA, Schechter SJ, Sundel RP, et al. Thalidomide for severe systemic onset juvenile rheumatoid arthritis: a multicenter study. The Journal of Pediatrics. 2004;145(6):856–857.
  • Klepser TB, Kelly MW. Metformin hydrochloride: an antihyperglycemic agent. Am J Health Syst Pharm. 1997;54(8):893–903.
  • Negrotto L, Farez MF, Correale J. Immunologic effects of metformin and pioglitazone treatment on metabolic syndrome and multiple sclerosis. JAMA Neurol. 2016; 73(5):520–528.
  • Kang KY, Kim Y-K, Yi H, Kim J, et al. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int Immunopharmacol. 2013; 16(1):85–92.
  • Zhang L, Zhang J, Ye Z, et al. Pharmacology of ME-344, a novel cytotoxic isoflavone. Adv Cancer Res. 2019;142:187–207.
  • Alvero AB, Montagna MK, Chen R, et al. NV-128, a novel isoflavone derivative, induces caspase-independent cell death through the akt/mammalian target of rapamycin pathway. Cancer. 2009;115(14):3204–3216. Jul

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