Novel insight into drug repositioning: Methylthiouracil as a case in point

Pharmacological Research

Volumn 99, Issue , 2015, Pages 185-193

  Baek, Moon Chang ^a   Jung, Byeongjin ^b   Kang, Hyejin ^b   Lee, Hyun Shik ^b   Bae, Jong Sup ^b  

^a Kyungpook National University School of Medicine   (South Korea)

^b Kyungpook National University   (South Korea)

Author keywords

Anti inflammatory reagent; Drug repositioning; Methylthiouracil; sPLA2 IIA

Indexed keywords

CYTOSOLIC PHOSPHOLIPASE A2; CYTOSOLIC PHOSPHOLIPASE A2 ALPHA; DOXYCYCLINE; METHYLTHIOURACIL; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; SECRETORY PHOSPHOLIPASE A2; THALIDOMIDE; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; ANTITHYROID AGENT; BIOLOGICAL MARKER; MITOGEN ACTIVATED PROTEIN KINASE;

ARTICLE; CELL ACTIVATION; DRUG EFFECT; DRUG INDICATION; DRUG INDUSTRY; DRUG REPOSITIONING; DRUG RESEARCH; DRUG STRUCTURE; ENDOTOXEMIA; ENZYME ACTIVITY; ERYTHEMA NODOSUM LEPROSUM; HUMAN; INFLAMMATORY DISEASE; NONHUMAN; PATENT; PERIODONTITIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RHEUMATOID ARTHRITIS; TREATMENT PLANNING; UMBILICAL VEIN ENDOTHELIAL CELL; VASCULITIS; ANIMAL; ANTAGONISTS AND INHIBITORS; ARTHRITIS, RHEUMATOID; DRUG DEVELOPMENT; ERYTHEMA NODOSUM; LEPROSY, LEPROMATOUS; PROCEDURES; TRENDS;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTITHYROID AGENTS; ARTHRITIS, RHEUMATOID; BIOMARKERS; DOXYCYCLINE; DRUG DISCOVERY; DRUG REPOSITIONING; ERYTHEMA NODOSUM; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; INTELLECTUAL PROPERTY; LEPROSY, LEPROMATOUS; METHYLTHIOURACIL; PERIODONTITIS; PHOSPHOLIPASES A2, SECRETORY; THALIDOMIDE; VASCULITIS;

EID: 84937577473     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2015.06.008     Document Type: Review

References (106)

1. B.M. Padhy, and Y.K. Gupta Drug repositioning: re-investigating existing drugs for new therapeutic indications J Postgrad Med 57 2011 153 160
2. J.L. Medina-Franco, M.A. Giulianotti, G.S. Welmaker, and R.A. Houghten Shifting from the single to the multitarget paradigm in drug discovery Drug Discov Today 18 2013 495 501
3. J.L. Furman, and M. MacGarvie Academic collaboration and organizational innovation: the development of research capabilities in the US pharmaceutical industry, 1927-1946∗ Ind Corp Change 18 2009 929 961
4. H.J. Federsel Chemical process research and development in the 21st century: challenges, strategies, and solutions from a pharmaceutical industry perspective Acc Chem Res 42 2009 671 680
5. S. Shah, and H.J. Federoff Drug discovery dilemma and cura quartet collaboration Drug Discov Today 14 2009 1006 1010
6. B. Munos Lessons from 60 years of pharmaceutical innovation Nat Rev Drug Discov 8 2009 959 968
7. R.C. Renaud, and H. Xuereb Erectile-dysfunction therapies Nat Rev Drug Discov 1 2002 663 664
8. V.C. Jordan, E. Phelps, and J.U. Lindgren Effects of anti-estrogens on bone in castrated and intact female rats Breast Cancer Res Treat 10 1987 31 35
9. S.B. Wheatcroft Teaching an old drug new tricks: can paroxetine ease the burden of cardiovascular disease in diabetes Diabetes 62 2013 698 700
10. T.T. Ashburn, and K.B. Thor Drug repositioning: identifying and developing new uses for existing drugs Nat Rev Drug Discov 3 2004 673 683
11. X. Liu, F. Zhu, X.H. Ma, Z. Shi, S.Y. Yang, Y.Q. Wei, and et al. Predicting targeted polypharmacology for drug repositioning and multi-target drug discovery Curr Med Chem 20 2013 1646 1661
12. K.I. Kaitin Deconstructing the drug development process: the new face of innovation Clin Pharmacol Ther 87 2010 356 361
13. E.L. Tobinick The value of drug repositioning in the current pharmaceutical market Drug News Perspect 22 2009 119 125
14. K.A. O'Connor, and B.L. Roth Finding new tricks for old drugs: an efficient route for public-sector drug discovery Nat Rev Drug Discov 4 2005 1005 1014
15. H.M. Vesterinen, P. Connick, C.M.J. Irvine, E.S. Sena, K.J. Egan, G.G. Carmichael, and et al. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis PLOS ONE 2015 10
16. A. Corbett, G. Williams, and C. Ballard Drug repositioning: an opportunity to develop novel treatments for Alzheimer's disease Pharmaceuticals (Basel) 6 2013 1304 1321
17. Cutting edge information Pharmaceutical product relaunch: preserving market share through line extension and new market entry strategies 2007 https://www.cuttingedgeinfo.com/research/portfolio-management/product-relaunch/
18. J.M. Miyasaki, W. Martin, O. Suchowersky, W.J. Weiner, and A.E. Lang Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review: report of the quality standards subcommittee of the American Academy of Neurology Neurology 58 2002 11 17
19. M.J. Thorpy New paradigms in the treatment of restless legs syndrome Neurology 64 2005 S28 S33
20. V. Suvarna Phase iv of drug development Perspect Clin Res 1 2010 57 60
21. H.J. Demonaco, A. Ali, and E. Hippel The major role of clinicians in the discovery of off-label drug therapies Pharmacotherapy 26 2006 323 332
22. N. Kumar, U. Sharma, C. Singh, and B. Singh Thalidomide chemistry, therapeutic potential and oxidative stress induced teratogenicity Curr Top Med Chem 12 2012 1436 1455
23. B. Lusk Dark remedy: the impact of thalidomide and its revival as a vital medicine Nurs Hist Rev 14 2006 271 272
24. L. Murch Eortc-nci-aacr - 18th symposium - molecular targets and cancer therapeutics. New approaches in treating cancer IDrugs 10 2007 8 10
25. I. Collins, and P. Workman New approaches to molecular cancer therapeutics Nat Chem Biol 2 2006 689 700
26. M. Ohlmeyer, and M.M. Zhou Integration of small-molecule discovery in academic biomedical research Mt Sinai J Med 77 2010 350 357
27. E. Zerhouni Medicine. The NIH roadmap Science 302 2003 63 72
28. C. Schubert Matchmaking service links up researchers to wallflower drugs Nat Med 16 2010 7
29. K. Marusina, D.J. Welsch, L. Rose, D. Brock, and N. Bahr The ctsa pharmaceutical assets portal - a public-private partnership model for drug repositioning Drug Discov Today Ther Strateg 8 2011 77 83
30. T.I. Oprea, and J. Mestres Drug repurposing: far beyond new targets for old drugs AAPS J 14 2012 759 763
31. J.L. Cummings, and K. Zhong Repackaging fda-approved drugs for degenerative diseases: promises and challenges Expert Rev Clin Pharmacol 7 2014 161 165
32. C.S. Hemphill, and B. Sampat Drug patents at the Supreme Court Science 339 2013 1386 1387
33. A.K. Rai, and G. Rice Use patents can be useful: the case of rescued drugs Sci Trans Med 2014 6
34. J. Ratnam, B. Zdrazil, D. Digles, E. Cuadrado-Rodriguez, J.M. Neefs, H. Tipney, and et al. The application of the open pharmacological concepts triple store (open phacts) to support drug discovery research PLOS ONE 9 2014 e115460
35. L. Sjostrom, L. Laurell, A. Hugoson, and J.P. Hakansson Periodontal conditions in adults with rheumatoid arthritis Community Dent Oral Epidemiol 17 1989 234 236
36. K. Tolo, and L. Jorkjend Serum antibodies and loss of periodontal bone in patients with rheumatoid arthritis J Clin Periodontol 17 1990 288 291
37. F.B. Mercado, R.I. Marshall, A.C. Klestov, and P.M. Bartold Relationship between rheumatoid arthritis and periodontitis J Periodontol 72 2001 779 787
38. F. Mercado, R.I. Marshall, A.C. Klestov, and P.M. Bartold Is there a relationship between rheumatoid arthritis and periodontal disease J Clin Periodontol 27 2000 267 272
39. U.R. Kasser, C. Gleissner, F. Dehne, A. Michel, B. Willershausen-Zonnchen, and W.W. Bolten Risk for periodontal disease in patients with longstanding rheumatoid arthritis Arthritis Rheum 40 1997 2248 2251
40. N.S. Ramamurthy, R.A. Greenwald, M.Y. Celiker, and E.Y. Shi Experimental arthritis in rats induces biomarkers of periodontitis which are ameliorated by gene therapy with tissue inhibitor of matrix metalloproteinases J Periodontol 76 2005 229 233
41. Guidelines ACoRAHCoC Guidelines for monitoring drug therapy in rheumatoid arthritis Arthritis Rheum 39 1996 713 722
42. Guidelines ACoRAHCoC Guidelines for monitoring drug therapy in rheumatoid arthritis Arthritis Rheum 39 1996 723 731
43. G. Sapna, S. Gokul, and K. Bagri-Manjrekar Matrix metalloproteinases and periodontal diseases Oral Dis 20 2014 538 550
44. L.M. Golub, H.M. Lee, G. Lehrer, A. Nemiroff, T.F. McNamara, R. Kaplan, and et al. Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action J Periodontal Res 18 1983 516 526
45. L.M. Golub, T.F. McNamara, G. D'Angelo, R.A. Greenwald, and N.S. Ramamurthy A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity J Dent Res 66 1987 1310 1314
46. M.S. Reddy, N.C. Geurs, and J.C. Gunsolley Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review Ann Periodontol 8 2003 12 37
47. P.M. Preshaw, A.F. Hefti, M.J. Novak, B.S. Michalowicz, B.L. Pihlstrom, R. Schoor, and et al. Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planning in chronic periodontitis: a multicenter trial J Periodontol 75 2004 1068 1076
48. B.C. Tilley, G.S. Alarcon, S.P. Heyse, D.E. Trentham, R. Neuner, D.A. Kaplan, and et al. Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. Mira trial group Ann Intern Med 122 1995 81 89
49. S.A. Voils, M.E. Evans, M.T. Lane, R.H. Schosser, and R.P. Rapp Use of macrolides and tetracyclines for chronic inflammatory diseases Ann Pharmacother 39 2005 86 94
50. J.R. Elliott, G.A. Paulsen, J.A. Mallek, T.R. Mikuls, C.A. Weaver, S. Glickstein, and et al. Treatment of early sero-positive rheumatoid arthritis: doxycycline with methotrexate versus methotrexate alone Arthritis Rheum 48 2003 S654-S654
51. M.E. Ryan, R.A. Greenwald, and L.M. Golub Potential of tetracyclines to modify cartilage breakdown in osteoarthritis Curr Opin Rheumatol 8 1996 238 247
52. G.N. Smith Jr., E.A. Mickler, K.A. Hasty, and K.D. Brandt Specificity of inhibition of matrix metalloproteinase activity by doxycycline: Relationship to structure of the enzyme Arthritis Rheum 42 1999 1140 1146
53. C.S. Westhoff, D. Freudiger, P. Petrow, C. Seyfert, J. Zacher, J. Kriegsmann, and et al. Characterization of collagenase 3 (matrix metalloproteinase 13) messenger RNA expression in the synovial membrane and synovial fibroblasts of patients with rheumatoid arthritis Arthritis Rheum 42 1999 1517 1527
54. I. Tchetverikov, H.K. Ronday, B. Van El, G.H. Kiers, N. Verzijl, J.M. TeKoppele, and et al. Mmp profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis Ann Rheum Dis 63 2004 881 883
55. A.R. Amin, M.G. Attur, G.D. Thakker, P.D. Patel, P.R. Vyas, R.N. Patel, and et al. A novel mechanism of action of tetracyclines: effects on nitric oxide synthases Proc Natl Acad Sci U S A 93 1996 14014 14019
56. J. Liu, C.A. Kuszynski, and B.T. Baxter Doxycycline induces fas/fas ligand-mediated apoptosis in jurkat t lymphocytes Biochem Biophys Res Commun 260 1999 562 567
57. T. Krakauer, and M. Buckley Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines Antimicrob Agents Chemother 47 2003 3630 3633
58. J.R. O'Dell, J.R. Elliott, J.A. Mallek, T.R. Mikuls, C.A. Weaver, S. Glickstein, and et al. Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate alone Arthritis Rheum 54 2006 621 627
59. E.P. Sampaio, E.N. Sarno, R. Galilly, Z.A. Cohn, and G. Kaplan Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes J Exp Med 173 1991 699 703
60. D.R. Lide, and G.W.A. Milne Properties of organic compounds. CRC Press database 1996 CRC Press Boca Raton, FL
61. Medical products agency. Uppsala, 2000.
62. Medicines control agency. London, 2000.
63. Medicines evaluation board agency. The Hague, 2000.
64. D.A. Six, and E.A. Dennis The expanding superfamily of phospholipase a(2) enzymes: classification and characterization Biochim Biophys Acta 1488 2000 1 19
65. I. Kudo, and M. Murakami Phospholipase a2 enzymes Prostaglandins Other Lipid Mediat 68/69 2002 3 58
66. M. Murakami, S. Shimbara, T. Kambe, H. Kuwata, M.V. Winstead, J.A. Tischfield, and et al. The functions of five distinct mammalian phospholipase a2s in regulating arachidonic acid release. Type iia and type v secretory phospholipase a2s are functionally redundant and act in concert with cytosolic phospholipase a2 J Biol Chem 273 1998 14411 14423
67. M. Menschikowski, A. Hagelgans, and G. Siegert Secretory phospholipase a2 of group iia: is it an offensive or a defensive player during atherosclerosis and other inflammatory diseases Prostaglandins Other Lipid Mediat 79 2006 1 33
68. C.M. Mounier, T.M. Hackeng, F. Schaeffer, G. Faure, C. Bon, and J.H. Griffin Inhibition of prothrombinase by human secretory phospholipase a2 involves binding to factor xa J Biol Chem 273 1998 23764 23772
69. S.E. Goldblum, T.W. Brann, X. Ding, J. Pugin, and P.S. Tobias Lipopolysaccharide (lps)-binding protein and soluble cd14 function as accessory molecules for lps-induced changes in endothelial barrier function, in vitro J Clin Invest 93 1994 692 702
70. J.A. Russell Management of sepsis N Engl J Med 355 2006 1699 1713
71. P. Baluk, L.C. Yao, J. Feng, T. Romano, S.S. Jung, J.L. Schreiter, and et al. Tnf-alpha drives remodeling of blood vessels and lymphatics in sustained airway inflammation in mice J Clin Invest 119 2009 2954 2964
72. D. Mehta, and A.B. Malik Signaling mechanisms regulating endothelial permeability Physiol Rev 86 2006 279 367
73. M. Alaoui-El-Azher, Y. Wu, N. Havet, A. Israel, A. Lilienbaum, and L. Touqui Arachidonic acid differentially affects basal and lipopolysaccharide-induced spla(2)-iia expression in alveolar macrophages through nf-kappab and ppar-gamma-dependent pathways Mol Pharmacol 61 2002 786 794
74. H. Kuwata, C. Fujimoto, E. Yoda, S. Shimbara, Y. Nakatani, S. Hara, and et al. A novel role of group vib calcium-independent phospholipase a2 (ipla2gamma) in the inducible expression of group iia secretory pla2 in rat fibroblastic cells J Biol Chem 282 2007 20124 20132
75. J.T. Flynn, and H. Hoff 3rd. Lipopolysaccharide induces time-dependent increases in prostaglandin h synthase-2 and cytosolic phospholipase a2 MRNA in cultured human microvessel-derived endothelial cells Shock 4 1995 433 440
76. S. Oka, and H. Arita Inflammatory factors stimulate expression of group ii phospholipase a2 in rat cultured astrocytes. Two distinct pathways of the gene expression J Biol Chem 266 1991 9956 9960
77. E.A. Dennis The growing phospholipase a2 superfamily of signal transduction enzymes Trends Biochem Sci 22 1997 1 2
78. W. Pruzanski, and P. Vadas Phospholipase a2 - a mediator between proximal and distal effectors of inflammation Immunol Today 12 1991 143 146
79. C. Waydhas, D. Nast-Kolb, K.H. Duswald, P. Lehnert, and L. Schweiberer Prognostic value of serum phospholipase a in the multitraumatized patient Klin Wochenschr 67 1989 203 206
80. T. Nakano, O. Ohara, H. Teraoka, and H. Arita Glucocorticoids suppress group ii phospholipase a2 production by blocking MRNA synthesis and post-transcriptional expression J Biol Chem 265 1990 12745 12748
81. R.M. Crowl, T.J. Stoller, R.R. Conroy, and C.R. Stoner Induction of phospholipase a2 gene expression in human hepatoma cells by mediators of the acute phase response J Biol Chem 266 1991 2647 2651
82. R.L. Carasso, J. Vardi, J.M. Rabay, U. Zor, and M. Streifler Measurement of prostaglandin e2 in cerebrospinal fluid in patients suffering from stroke J Neurol Neurosurg Psychiatry 40 1977 967 969
83. W. Gao, A. Schmidtko, I. Wobst, R. Lu, C. Angioni, and G. Geisslinger Prostaglandin d2 produced by hematopoietic prostaglandin d synthase contributes to lps-induced fever J Physiol Pharmacol 60 2009 145 150
84. J.V. Bonventre, Z. Huang, M.R. Taheri, E. O'Leary, E. Li, M.A. Moskowitz, and et al. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase a2 Nature 390 1997 622 625
85. W. Tian, G.T. Wijewickrama, J.H. Kim, S. Das, M.P. Tun, N. Gokhale, and et al. Mechanism of regulation of group iva phospholipase a2 activity by ser727 phosphorylation J Biol Chem 283 2008 3960 3971
86. K. Christov, and R. Raichev Thyroid carcinogenesis in hamsters after treatment with 131-iodine and methylthiouracil Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 77 1972 171 179
87. J. Moll, E. Martens, and H.G. Jansen Development of goitre after methylthiouracil treatment of mice with hypothalamic lesions J Endocrinol 45 1969 483 488
88. R. Schaffer, and H.A. Muller On the development of metastasizing tumors of the rat thyroid gland after combined administration of nitrosomethylurea and methylthiouracil J Cancer Res Clin Oncol 96 1980 281 285
89. J.A. Buras, B. Holzmann, and M. Sitkovsky Animal models of sepsis: setting the stage Nat Rev Drug Discov 4 2005 854 865
90. K.H. Diehl, R. Hull, D. Morton, R. Pfister, Y. Rabemampianina, D. Smith, and et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes J Appl Toxicol 21 2001 15 23
91. M.E. Astiz, and E.C. Rackow Septic shock Lancet 351 1998 1501 1505
92. D.S. Grass, R.H. Felkner, M.Y. Chiang, R.E. Wallace, T.J. Nevalainen, C.F. Bennett, and et al. Expression of human group ii pla2 in transgenic mice results in epidermal hyperplasia in the absence of inflammatory infiltrate J Clin Invest 97 1996 2233 2241
93. G. Beck, B.A. Yard, J. Schulte, M. Haak, K. van Ackern, F.J. van der Woude, and et al. Secreted phospholipases a2 induce the expression of chemokines in microvascular endothelium Biochem Biophys Res Commun 300 2003 731 737
94. J.H. Scharf, R. Schmidt, D. Marzotko, E. Mantel, and C. Wanka Side effects of single and combined administration of methylthiouracil, p-hydroxypropiophenone, diiodothyrosine and alloxan on the blood cell count, hemoglobin content and blood sugar level in albino rats Endokrinologie 47 1965 161 171
95. R.S. Bahn, H.S. Burch, D.S. Cooper, J.R. Garber, C.M. Greenlee, I.L. Klein, and et al. The role of propylthiouracil in the management of Graves' disease in adults: Report of a meeting jointly sponsored by the American thyroid association and the food and drug administration Thyroid 19 2009 673 674
96. B. Readhead, and J. Dudley Translational bioinformatics approaches to drug development Adv Wound Care (New Rochelle) 2 2013 470 489
97. J.P. Hughes, S. Rees, S.B. Kalindjian, and K.L. Philpott Principles of early drug discovery Br J Pharmacol 162 2011 1239 1249
98. D. Bradley Why big pharma needs to learn the three 'r's Nat Rev Drug Discov 4 2005 446
99. M.S. Boguski, K.D. Mandl, and V.P. Sukhatme Drug discovery. Repurposing with a difference Science 324 2009 1394 1395
100. B.S. Appleby, D. Nacopoulos, N. Milano, K. Zhong, and J.L. Cummings A review: treatment of Alzheimer's disease discovered in repurposed agents Dement Geriatr Cogn Disord 35 2013 1 22
101. G. Jin, and S.T. Wong Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines Drug Discov Today 19 2014 637 644
102. J.S. Bae, W. Lee, J.O. Nam, J.E. Kim, S.W. Kim, and I.S. Kim Transforming growth factor beta-induced protein promotes severe vascular inflammatory responses Am J Respir Crit Care Med 189 2014 779 786
103. S.K. Ku, M.S. Han, M.Y. Lee, Y.M. Lee, and J.S. Bae Inhibitory effects of oroxylin a on endothelial protein c receptor shedding in vitro and in vivo BMB Rep 47 2014 336 341
104. S.K. Ku, and J.S. Bae Antithrombotic activities of sulforaphane via inhibiting platelet aggregation and fiia/fxa Arch Pharm Res 37 2014 1454 1463
105. J.S. Bae, and A.R. Rezaie Thrombin and activated protein c inhibit the expression of secretory group iia phospholipase a(2) in the tnf-alpha-activated endothelial cells by epcr and par-1 dependent mechanisms Thromb Res 125 2010 e9 e15
106. Y. Shimoyama, R. Sakamoto, T. Akaboshi, M. Tanaka, and K. Ohtsuki Characterization of secretory type iia phospholipase a2 (spla2-iia) as a glycyrrhizin (gl)-binding protein and the gl-induced inhibition of the ck-ii-mediated stimulation of spla2-iia activity in vitro Biol Pharm Bull 24 2001 1004 1008