Computational platform Way2Drug: from the prediction of biological activity to drug repurposing

Abstract

The Way2Drug informational-computational platform (www.way2drug.com/dr) provides access to the data on drugs approved for medicinal use in the USA and Russian Federation, as well as computational possibilities for the prediction of biological activity of drug-like organic compounds. Currently realized computational tools of the platform, which allow one to predict several thousands of biological activity types, including the interaction with molecular targets, pharmacotherapeutic and side effects, metabolism, acute toxicity for rats, cytotoxicity, influence on gene expression, and other properties characterizing the evaluation how promising are particular drug-like compounds as potential pharmaceuticals, are reviewed. Using the Way2Drug platform, one can not only select the most promising "hits" for the synthesis and testing of biological activity but also reveal new indications for the launched drugs.

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References

  1. 1.

    G. M. Barenboim, A. G. Malenkov, Biologicheski aktivnye veshchestva. Novye printsipy poiska [Biologically Active Substances. New Principles of Search], Nauka, Moscow, 1986, 363 pp. (in Russian).

    Google Scholar 

  2. 2.

    Thomson Reuters Integrity URL, https://integrity.thomsonpharma.com.

  3. 3.

    G. R. Zimmermann, J. Lehár, C. T. Keith, Drug Discov. Today, 2007, 12,34.

    CAS  Article  Google Scholar 

  4. 4.

    R. M. Rydzewski, Real World Drug Discovery: A Chemist´s Guide to Biotech and Pharmaceutical Research, Elsevier, Oxford, 2008, 515 pp.

    Google Scholar 

  5. 5.

    M. S. Kinch, A. Haynesworth, S. L. Kinch, D. Hoyer, Drug Discov. Today, 2014, 19, 1033.

    CAS  Article  Google Scholar 

  6. 6.

    Pharmaceutical Sciences: Breakthroughs in Research and Practice, IGI Global, Hershey, 2016, 1584 pp.

  7. 7.

    H. A. Gaspar, I. I. Baskin, G. Marcou, D. Horvath, A. Varnek, J. Chem. Inf. Model., 2015, 55,84.

    CAS  Article  Google Scholar 

  8. 8.

    I. V. Tetko, O. Engkvist, H. Chen, Future Med. Chem., 2016, 8, 1801.

    CAS  Article  Google Scholar 

  9. 9.

    Chemical Abstracts Services URL, http://www.cas.org.

  10. 10.

    PubMed URL, https://www.ncbi.nlm.nih.gov/pubmed.

  11. 11.

    U.S. Patent and Trade Office URL, https://www.uspto.gov/ patents-application-process/search-patents.

  12. 12.

    PubChem URL, https://pubchem.ncbi.nlm.nih.gov.

  13. 13.

    S. Kim, P. A. Thiessen, E. E. Bolton, J. Chen, G. Fu, A. Gindulyte, L. Han, J. He, S. He, B. A. Shoemaker, J. Wang, B. Yu, J. Zhang, S. H. Bryant, Nucleic Acids Res., 2016, 44, D1202.

    CAS  Article  Google Scholar 

  14. 14.

    ChEMBL URL, https://www.ebi.ac.uk/chembl.

  15. 15.

    G. Papadatos, A. Gaulton, A. Hersey, J. P. Overington, J. Comput. Aided. Mol. Des., 2015, 29,885.

    CAS  Article  Google Scholar 

  16. 16.

    ChEBI URL, https://www.ebi.ac.uk/chebi.

  17. 17.

    J. Hastings, P. de Matos, A. Dekker, M. Ennis, B. Harsha, N. Kale, V. Muthukrishnan, G. Owen, S. Turner, M. Williams, C. Steinbeck, Nucl. Acids Res., 2012, 41, D456.

    Article  Google Scholar 

  18. 18.

    DrugBank URL, https://www.drugbank.ca/.

  19. 19.

    D. S. Wishart, C. Knox, A. C. Guo, S. Shrivastava, M. Hassanali, P. Stothard, Z. Chang, J. Woolsey, Nucleic Acids Res., 2006, 34, D668.

    CAS  Article  Google Scholar 

  20. 20.

    SIDER URL, http://sideeffects.embl.de/.

  21. 21.

    M. Kuhn, I. Letunic, L. J. Jensen, P. Bork, Nucleic Acids Res., 2015, 44, D1075.

    Article  Google Scholar 

  22. 22.

    D. A. Filimonov, V. V. Poroikov, J. Comput.-Aided Mol. Design, 2005, 19,705.

    CAS  Article  Google Scholar 

  23. 23.

    S. Ekins, Computer Applications in Pharmaceutical Research and Development, John Wiley and Sons, Weinheim, 2006, 805 pp.

    Google Scholar 

  24. 24.

    B. Goldakre, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients, Straus and Giroux, Farrar, 2013, 448 pp.

    Google Scholar 

  25. 25.

    V. M. Bezhentsev, D. S. Druzhilovskiy, S. M. Ivanov, D. A. Filimonov, G. N. Sastry, V. V. Poroikov, Pharm. Chem. J., 2017, 51,91.

    CAS  Article  Google Scholar 

  26. 26.

    V. Sh. Rubashkin, Predstavlenie i analiz smysla v intellektual´nykh informatsionnykh sistemakh [Representation and Analysis of the Sense in Intellectual Informational Systems], Nauka, Moscow, 1989, 190 pp. (in Russian).

    Google Scholar 

  27. 27.

    V. K. Finn, Voprosy Filosofii [Problems of Philosophy], 2014, No. 2, 83 (in Russian).

    Google Scholar 

  28. 28.

    I. V. Tetko, U. Maran, A. Tropsha, Mol. Inform., 2017, 36, 1600082.

    Article  Google Scholar 

  29. 29.

    H. Kubinyi, J. Braz. Chem. Soc., 2002, 13,717.

    CAS  Article  Google Scholar 

  30. 30.

    D. Stumpfe, Y. Hu, D. Dimova, J. Bajorath, J. Med. Chem., 2014, 57,18.

    CAS  Article  Google Scholar 

  31. 31.

    Y. Martin, J. I. Kofron, L. M. Traphagen, J. Med. Chem., 2002, 45, 4350.

    CAS  Article  Google Scholar 

  32. 32.

    K. Anusevicius, V. Mickevicius, M. Stasevych, V. Zvarych, O. Komarovska-Porokhnyavets, V. Novikov, O. Tarasova, T. Gloriozova, V. Poroikov, Res. Chem. Intermed., 2015, 41, 7517.

    CAS  Article  Google Scholar 

  33. 33.

    D. S. Druzhilovskiy, A. V. Rudik, D. A. Filimonov, A. A. Lagunin, T. A. Gloriozova, V. V. Poroikov, Russ. Chem. Bull., 2016, 65,384.

    CAS  Article  Google Scholar 

  34. 34.

    O. T. Devinyak, R. B. Lesyk, Curr. Comput. Aided Drug Des., 2016, 12,265.

    CAS  Article  Google Scholar 

  35. 35.

    D. A. Filimonov, V. V. Poroikov, E. I. Karaicheva, R. K. Kazaryan, A. P. Budunova, E. M. Mikhailovskii, A. V. Rudnitskikh, L. V. Goncharenko, Yu. V. Burov, Eksp. Klinich. Farmakol. [Experimental Clinical Pharmacology], 1995, 58, 56 (in Ruusian).

    CAS  Google Scholar 

  36. 36.

    D. A. Filimonov, A. A. Lagunin, T. A. Gloriozova, A. V. Rudik, D. S. Druzhilovskiy, P. V. Pogodin, V. V. Poroikov, Chem. Heterocycl. Compds, 2014, 50,444.

    CAS  Article  Google Scholar 

  37. 37.

    L. Vegner, A. Peragovics, L. Tombor, B. Jelinek, P. Czobor, A. Bender, Z. Simon, A. Málnási-Csizmadia, J. Med. Chem., 2013, 56, 8377.

    CAS  Article  Google Scholar 

  38. 38.

    A. Lagunin, A. Stepanchikova, D. Filimonov, V. Poroikov, Bioinformatics, 2000, 16,747.

    CAS  Article  Google Scholar 

  39. 39.

    Yu. V. Burov, L. V. Korol´chenko, V. V. Poroikov, Byull. Vsesoyuzn. nauch. tsentra po bezopasnosti biologicheski aktivnykh veshchestv [Bulletin of the All-Union Scientific Center on Safety of Biologically Active Substances], 1990, No. 1, 4 (in Russian).

    Google Scholar 

  40. 40.

    V. V. Poroikov, D. A. Filimonov, A. P. Budunova, NauchnoTekhn. Inform., Ser. 2 [Scientific Technical Information, Ser. 2], 1993, No. 6, 11 (in Russian).

    Google Scholar 

  41. 41.

    V. V. Poroikov, in Meditsinskaya biofizika. Biologicheskie ispytaniya khimicheskikh soedinenii [Medical Biophysics. Biological Assays of Chemical Compounds], Meditsina, Moscow, 2005, 546 pp. (in Russian).

    Google Scholar 

  42. 42.

    V. V. Poroikov, D. A. Filimonov, Yu. V. Borodina, A. A. Lagunin, A. Kos, J. Chem. Inform. Comput. Sci., 2000, 40, 1349.

    CAS  Article  Google Scholar 

  43. 43.

    A. V. Sadym, A. A. Lagunin, D. A. Filimonov, V. V. Poroikov, Pharm. Chem. J., 2002, 36,538.

    CAS  Article  Google Scholar 

  44. 44.

    A. Sadym, A. Lagunin, D. Filimonov, V. Poroikov, SAR and QSAR Environ. Res., 2003, 14,339.

    CAS  Article  Google Scholar 

  45. 45.

    A. Geronikaki, D. Druzhilovskiy, A. Zakharov, V. Poroikov, SAR and QSAR Environ. Res., 2008, 19,27.

    CAS  Article  Google Scholar 

  46. 46.

    D. S. Druzhilovskiy, A. V. Rudik, D. A. Filimonov, V. V. Poroikov, in Mater. IX Mezhdunar. Kongressa "Biotekhnologiya: sostoyanie i perspektivy razvitiya" [Proc. IX Intern. Congress "Biotechnology: State and Prospects of Development"], OOO RED GRUPP, Moscow, 2017, Vol. 1, p. 367 (in Russian).

    Google Scholar 

  47. 47.

    A. Ariffin, N. A. Rahman, W. A. Yehye, A. A. Alhadi, F. A. Kadir, Eur. J. Med. Chem., 2014, 87,564.

    CAS  Article  Google Scholar 

  48. 48.

    H. Patel, Y. Sonawane, R. Jagtap, K. Dhangar, N. Thapliyal, S. Surana, M. Noolvi, M. S. Shaikh, R. A. Rane, R. Karpoormath, Bioorg. Med. Chem. Lett., 2015, 25, 1938.

    CAS  Article  Google Scholar 

  49. 49.

    T. G. Tolstikova, E. A. Morozova, S. V. Sysolyatin, A. I. Kalashnikov, Yu. I. Zhukova, V. N. Surmachev, Khimiya v Interesakh Ustoichivogo Razvitiya [Chemistry in Interests of Stable Development], 2010, No. 18, 511 (in Russian).

    CAS  Google Scholar 

  50. 50.

    RF Patent No. 2558148; Byul. Izobret. [Invention Bulletin], 2015, 21 (in Russian).

  51. 51.

    RF Patent No. 2565766; Byul. Izobret. [Invention Bulletin], 2015, 29 (in Russian).

  52. 52.

    Way2Drug URL, http://way2drug.com.

  53. 53.

    D. A. Filimonov, A. V. Zakharov, A. A. Lagunin, V. V. Poroikov, SAR and QSAR Environ. Res., 2009, 20,679.

    CAS  Article  Google Scholar 

  54. 54.

    A. Lagunin, A. Zakharov, D. Filimonov, V. Poroikov, Mol. Inform., 2011, 30,241.

    CAS  Article  Google Scholar 

  55. 55.

    A. V. Zakharov, A. A. Lagunin, D. A. Filimonov, V. V. Poroikov, Chem. Res. Toxicol., 2012, 25, 2378.

    CAS  Article  Google Scholar 

  56. 56.

    GUSAR EnvironTox URL, http://www.way2drug.com/ gusar/environmental.html.

  57. 57.

    V. V. Goncharuk, A. L. Buben, O. A. Borisenok, V. I. Kozlovskii, I. M. Pun´ko, V. P. Vdovichenko, K. D. Praliev, Eksp. Klinich. Farmakol. [Experimental Clinical Pharmacology], 2016, 79, 7 (in Russian).

    CAS  Google Scholar 

  58. 58.

    S. H. Unnissa, D. Rajan, J. Chem. Pharm. Res., 2016, 8,999.

    CAS  Google Scholar 

  59. 59.

    E. V. Fedorova, A. V. Buryakina, A. V. Zakharov, D. A. Filimonov, A. A. Lagunin, V. V. Poroikov, PLoS One, 2014, 9, e100386.

    Article  Google Scholar 

  60. 60.

    A. Lagunin, S. Ivanov, A. Rudik, D. Filimonov, V. Poroikov, Bioinformatics, 2013, 29, 2062.

    CAS  Article  Google Scholar 

  61. 61.

    DIGEP Pred URL, http://www.way2drug.com/ge/.

  62. 62.

    V. Konova, A. Lagunin, P. Pogodin, E. Kolotova, A. Shtil, V. Poroikov, SAR and QSAR Environ. Res., 2015, 26,595.

    CAS  Article  Google Scholar 

  63. 63.

    PASS CLC Pred URL, http://www.way2drug.com/ Cell-line/.

  64. 64.

    P. V. Pogodin, A. A. Lagunin, D. A. Filimonov, V. V. Poroikov, SAR & QSAR Environ. Res., 2015, 26,783.

    CAS  Article  Google Scholar 

  65. 65.

    KinScreen URL, http://www.way2drug.com/kinscreen.

  66. 66.

    M. Nand, P. Maiti, R. Pant, M. Kumari, S. Chandra, V. Pande, Bioinformation, 2016, 12,311.

    Article  Google Scholar 

  67. 67.

    A. Thomas, P. K. J. Prashob, N. Chandramohanakumar, Int. J. Pharmacogn. Phytochem. Res., 2016, 8, 1828.

    Google Scholar 

  68. 68.

    A. V. Rudik, A. V. Dmitriev, A. A. Lagunin, D. A. Filimonov, V. V. Poroikov, J. Chem. Inform. Model., 2014, 54,498.

    CAS  Article  Google Scholar 

  69. 69.

    A. Rudik, A. Dmitriev, A. Lagunin, D. Filimonov, V. Poroikov, Bioinformatics, 2015, 31, 2046.

    CAS  Article  Google Scholar 

  70. 70.

    A. Rudik, A. Dmitriev, A. Lagunin, D. Filimonov, V. Poroikov, J. Cheminform., 2016, 8,68.

    Article  Google Scholar 

  71. 71.

    MetaTox URL, http://way2drug.com/mg.

  72. 72.

    V. I. Dubovskaya, Ph. D. (Biol.) Thesis, Institute of Biomedical Chemistry, Moscow, 2017, 223 pp. (in Russian).

    Google Scholar 

  73. 73.

    A. L. Hopkins, Nat. Chem. Biol., 2008, 4,82.

    Article  Google Scholar 

  74. 74.

    O. N. Koborova, D. A. Filimonov, A. V. Zakharov, A. A. Lagunin, S. M. Ivanov, A. Kel, V. V. Poroikov, SAR and QSAR Environ. Res., 2009, 20,755.

    CAS  Article  Google Scholar 

  75. 75.

    S. M. Ivanov, A. A. Lagunin, P. V. Pogodin, D. A. Filimonov, V. V. Poroikov, Toxicol. Sci., 2015, 145,321.

    CAS  Article  Google Scholar 

  76. 76.

    S. Ekins, A. J. Williams, M. D. Krasowski, J. S. Freundlich, Drug Discov. Today, 2011, 16,298.

    Article  Google Scholar 

  77. 77.

    J. Langedijk, A. K. Mantel-Teeuwisse, D. S. Slijkerman, M.-H. D. B. Schutjens, Drug Discov. Today, 2015, 20, 1027.

    Article  Google Scholar 

  78. 78.

    T. T. Ashburn, K. B. Thor, Nat. Rev. Drug Discov., 2004, 3,673.

    CAS  Article  Google Scholar 

  79. 79.

    D. Cavalla, Nat. Rev. Drug Discov., 2009, 8,849.

    CAS  Article  Google Scholar 

  80. 80.

    D. R. Flower, J. Pharmacovigilance, 2013, 1, 1000e103.

    Article  Google Scholar 

  81. 81.

    S. Naylor, J. M. Schonfeld, Drug Discov. World, 2014, 15,49.

    Google Scholar 

  82. 82.

    D. Cavalla, Drug Discov. Today, 2013, 18,523.

    Article  Google Scholar 

  83. 83.

    C. L. Bellera, D. E. Balcazar, M. C. Vanrell, A. F. Casassa, P. H. Palestro, L. Gavernet, C. A. Labriola, J. Gálvez, L. E. Bruno-Blanch, P. S. Romano, C. Carrillo, A. Talevi, Eur. J. Med. Chem., 2015, 93,338.

    CAS  Article  Google Scholar 

  84. 84.

    T. I. Oprea, J. P. Overington, Drug Repurp., Resc. Reposit., 2015, 1,28.

    Google Scholar 

  85. 85.

    S. A. Kryzhanovskii, R. M. Salimov, A. A. Lagunin, D. A. Filimonov, T. A. Gloriozova, V. V. Poroikov, Pharmaceut. Chem. J., 2012, 45,605.

    CAS  Article  Google Scholar 

  86. 86.

    Y. Gao, R. O´Caoimh, L. Healy, D. M. Kerins, J. Eustace, G. Guyatt, D. Sammon, D. W. Molloy, BMJ Open, 3, e002881.

  87. 87.

    FDA approved drugs URL, http://www.way2drug.com/dr/ int_fda_aprooved.php.

  88. 88.

    Farmatsevticheskie substantsii zaregistrirovannye v RF [Pharmaceutical Substances Registered in the Russian Federation] URL, http://www.way2drug.com/dr/russian_drug.php (in Russian).

  89. 89.

    D. Fourches, E. Muratov, A. Tropsha, J. Chem. Inf. Model., 2010, 50, 1189.

    CAS  Article  Google Scholar 

  90. 90.

    D. Fourches, E. Muratov, A. Tropsha, Nat. Chem. Biol., 2015, 11,535.

    CAS  Article  Google Scholar 

  91. 91.

    D. Fourches, E. Muratov, A. Tropsha, J. Chem. Inf. Model., 2016, 56, 1243.

    CAS  Article  Google Scholar 

  92. 92.

    Registr lekarstvennykh sredstv Rossii [List of Pharmaceuticals in Russia] URL, http://www.rlsnet.ru/ (in Russian).

  93. 93.

    A. Dalby, J. G. Nourse, W. D. Hounshell, A. K. I. Gushurst, D. L. Grier, B. A. Leland, J. Laufer, J. Chem. Inf. Comput. Sci., 1992, 32,244.

    CAS  Article  Google Scholar 

  94. 94.

    Perechen´ iz 96 prioritetnykh biomishenii dlya razrabotki lekarstv v Rossii [List of 96 Priority Biotargets for the Development of Drugs in Russia] URL, http://www.garant.ru/products/ipo/prime/doc/71320680/ (in Russian).

  95. 95.

    Pharma-2020 URL, http://pharma-2020.ru/ (in Russian).

  96. 96.

    J. G. Cumming, A. M. Davis, S. Muresan, M. Haeberlein, H. Chen, Nat. Rev. Drug Discov., 2013, 12,948.

    CAS  Article  Google Scholar 

  97. 97.

    A. Cherkasov, E. N. Muratov, D. Fourches, A. Varnek, I. I. Baskin, M. Cronin, J. Dearden, P. Gramatica, Y. C. Martin, R. Todeschini, V. Consonni, V. E. Kuz´min, R. Cramer, R. Benigni, C. Yang, J. Rathman, L. Terfloth, J. Gasteiger, A. Richard, A. Tropsha, J. Med. Chem., 2014, 57, 4977.

    CAS  Article  Google Scholar 

  98. 98.

    J. Gasteiger, Molecules, 2016, 21,151.

    Article  Google Scholar 

  99. 99.

    O. A. Tarasova, A. F. Urusova, D. A. Filimonov, M. C. Nicklaus, A. V. Zakharov, V. V. Poroikov, J. Chem. Inform. Model., 2015, 55, 1388.

    CAS  Article  Google Scholar 

  100. 100.

    SAR Creator URL, http://www.way2drug.com/dr/ substance.php.

  101. 101.

    ChemAxon URL, http://www.chemaxon.com.

  102. 102.

    D. Weininger, J. Chem. Inform. Comput. Sci., 1988, 28,31.

    CAS  Article  Google Scholar 

  103. 103.

    S. Heller, A. McNaught, S. Stein, D. Tchekhovskoi, I. Pletnev, J. Cheminform., 2012, 5,7.

    Article  Google Scholar 

  104. 104.

    MPDS URL, http://mpds.osdd.net/.

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Correspondence to D. S. Druzhilovskiy.

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Based on the Materials of the XX Mendeleev Congress on General and Applied Chemistry (September 26—30, 2016, Ekaterinburg).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1832—1841, October, 2017.

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Druzhilovskiy, D.S., Rudik, A.V., Filimonov, D.A. et al. Computational platform Way2Drug: from the prediction of biological activity to drug repurposing. Russ Chem Bull 66, 1832–1841 (2017). https://doi.org/10.1007/s11172-017-1954-x

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Keywords

  • informational-computational platform Way2Drug
  • analysis of structure—property relationships
  • prediction of biological activity profiles
  • drug repurposing