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October, 2013 UPDATE:

Screening Compounds

Fragment library


Research
Novel Jak3 inhibitor with high selectivity within the Jak kinase family

The Jak3-C interaction has proven to be of great interest due to its role in causing several different types of immunodeficiency disorders. The intense research in this area has important implications including treatment of Severe Combined Immunodeficiency and production of novel immunosuppressant drugs. Inhibitors of Jak3 could play a role in the treatment of autoimmune diseases and the prevention of transplant rejection.

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Development of human Protein Kinase CK2 inhibitors
  • Background


The role of the protein kinase CK2 is a transduction and enhancement of a wide range of cell growth and metabolic signals by phosphorylation of about 300 protein substrates. Abnormal CK2 expression and function are associated with a number of pathologies. These studies evoke strong interest to this enzyme as a target for anticancer, anti-inflammatory and anti-infectious drugs.

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Development of Human Protein Kinase ASK1 Inhibitors
In order to discover novel ASK1 inhibitors we have performed screening program, using both in silico and in vitro approaches. The virtual screening experiments were carried out targeting the ATP binding site of ASK1 by browsing the Otava Ltd. compound library of 156,000 organic compounds. The best-scored compounds have been selected and taken for the kinase assay study.
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Publications

Publications list of Otava's researchers:
 

 

PATENTS:

  1. W.F. Patton; S.M. Yarmoluk; P. Pande; V. Kovalska; L. Dai; K. Volkova; J. Coleman; M. Losytskyy; A. Ludlam; A. Balanda; D. Shen. Dyes for Analysis of Protein Aggregation // Patent Application Publication WO2011/065980 (A2), 03.06.2011.
  2. T.R. Berkelman, S.M. Yarmoluk, V.B. Kovalska, M.Yu. Losytskyy, K.D. Volkova. Use of squaraine dyes to visualize protein during separations // Patent Application US2008091015 A1, 17.04.2008; WO 2008/027821 A1, 06.03.2008.
  3. V.B. Kovalska; D.V. Kryvorotenko; M.Yu. Losytskyy; P. Nording; A. Rueck; B. Schoenenberger; S.M. Yarmoluk; F. Wahl. Detection of polyamino acids using trimethincyanine dyes // Patent Application US2006207881, 21.09.2006.
  4. Lesyk R.B., Zimenkovsky B.S., Yarmoluk S.M., Bdzhola V.H., Vovk О.І. Compound 5-[(4-chlorophenyl)methylidene]-2-(4-oxyanilino)-4,5-dihydrothiazol-4-one, which possess anticancer activity // Declaration patent on profitable model 2004031889. 15.02.2005. Bull. №2.
  5. Pat. UА68984 А, C07D215/00, 2004-08-16. Application of 4-substituted 3-carboxyquinolines as protein kinase CK2 inhibitors. Sapelkin V.M., Lukashov S.S., Golub A.G., Bdzhola V. G., Yakovenko O.Ya., Yarmoluk S.M., Dubinina G.G.
  6. Pat. UA69165 А, С07D215/00, 2004-08-16. Application of 4,5,6,7-tetrahalogeno-1,3-isoindolinediones as protein kinase CK2 inhibitors. Golub A.G., Yakovenko O.Ya., Yarmoluk S.M., Dubinina G.G., Bdzhola V. G., Prykhod’ko A.O.
  7. S.M. Yarmoluk, O.M. Kostenko, O.I. Tolmachev, O.S. Wolfbeis. Method and compounds for the fluorescent labelling of biomolecules and polymer particles // Patent Application US2003175988, 18. 09.2003.
  8. Pat. 61626A (UA). Cl. C07D207/444, A61K31/40. The structures with antitumor activity among 1-benzyl-3-chloro-4-anilino-2,5-dihydro-1H-2,5-pyrroledione derivatives. 17.11.2003. Appl. 2003032383. 19.03.2003. 10 pp. Tarnavsky S.S., Golovach S.M., Dubinina G.G., Yarmoluk S.M.

 

SELECTED RESEARCH ARTICLES:
  1. Volynets G., Bdzhola V., Golub A.,Synyugin A.,Chekanov M.,Kukharenko O.,Yarmoluk S.Rational Design of Apoptosis Signal-Regulating Kinase 1 Inhibitors: Discovering Novel Structural Scaffold. Eur J Med Chem. 2013, 61, 104-115.

  2. Golub A.G., Bdzhola V.G., Ostrynska O.V., Kyshenia I.V., Sapelkin V.M., Prykhod’ko A.O., Kukharenko O. P., Yarmoluk S.M.Discovery and characterization of synthetic 4’-hydroxyflavones - New CK2 inhibitors from flavone family. Bioorg. Med. Chem. 2013, 21, 6681-6689.

  3. Hunnigan K., Kulkarni S.S., Bdzhola V.G., Golub A.G., Yarmoluk S.M., Talele T.T. Identification of novel PARP-1 inhibitors by structure-based virtual screening. Bioorg. Med. Chem. Lett. 2013, 23, 5790-5794. 

  4. Golub AG, Gurukumar KR, Basu A, Bdzhola VG, Bilokin Y, Yarmoluk SM, Lee J-C, Talele TT, Nichols DB, Kaushik-Basu N. Discovery of New Scaffolds for Rational Design of HCV NS5B Polymerase Inhibitors. Eur J Med Chem. 2012, 58, 258-264.
  5. Martić S, Tackenburg S, Bilokin Y, Golub A, Bdzhola V, Yarmoluk S, Kraatz HB. Electrochemical screening of the indole/quinolone derivatives as potential protein kinase CK2 inhibitors. Anal Biochem. 2012, 421(2), 617-621.
  6. Structure-based discovery of novel flavonol inhibitors of human protein kinase CK2. Golub AG, Bdzhola VG, Kyshenia YV, Sapelkin VM, Prykhod'ko AO, Kukharenko OP, Ostrynska OV, Yarmoluk SM. Mol Cell Biochem. 2011, 356(1-2):107-115.
  7. Identification of 3H-naphtho[1,2,3-de]quinoline-2,7-diones as inhibitors of apoptosis signal-regulating kinase 1 (ASK1). Volynets GP, Chekanov MO, Synyugin AR, Golub AG, Kukharenko OP, Bdzhola VG, Yarmoluk SM. J Med Chem. 2011, 54(8):2680-2686.
  8. Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2. Golub AG, Bdzhola VG, Briukhovetska NV, Balanda AO, Kukharenko OP, Kotey IM, Ostrynska OV, Yarmoluk SM. Eur J Med Chem, 2011, 46(3):870-876.
  9. Treatment of cultured human astrocytes and vascular endothelial cells with protein kinase CK2 inhibitors induces early changes in cell shape and cytoskeleton. Kramerov AA, Golub AG, Bdzhola VG, Yarmoluk SM, Ahmed K, Bretner M, Ljubimov AV. Mol Cell Biochem, 2011, 349(1-2):125-137.
  10. Identification of ASK1 small-molecule inhibitors.Volynets GP, Bdzhola VG, Kukharenko OP, Yarmoluk SM. Ukr. Biochim. J. 2010; 82 (5): 41-50.
  11. Methods of structural bioinformatics. Volynets GP, Bdzhola VG, Yarmoluk SM. Biotechnology. 2010; 3 (4): 9-19.
  12. Search for FGFR1 inhibitors among chromone derivatives. Grischenko AA, Bdzhola VG, Kukharenko OP, Yarmoluk SM. Ukrainica Bioorganica Acta. 2009; 7 (2): 64-68.
  13. Protein kinase ASK1 as potential therapeutic target. Volynets GP, Bdzhola VG, Kukharenko OP, Sovetova OV, Yarmoluk SM. Biopolymers and Cell. 2009. 25 (3): 169-180.
  14. Evaluation of 4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones as inhibitors of human protein kinase CK2. A.G. Golub, O.Ya.Yakovenko, A.O. Prykhod'ko, S.S. Lukashov, V.G. Bdzhola, S.M. Yarmoluk. Biochimica et Biophysica Acta – 2008. – V.1784, № 1, P. 143–149.
  15. Synthesis and biologic evaluation of thienopyrimidinones inhibition activity against protein kinase CK2. Kotey IM, Balanda AO, Bdzhola VG, Lukashov SS, Kukharenko OP, Kharchenko VM, Yarmoluk SM. Ukrainica Bioorganica Acta. 2008. 6 (2): 3-9.
  16. Search for specific protein kinase СК2 inhibitors and vasoactive compounds among 5-amino-1,3-oxazoles derivatives. O.V. Shablykin, O.P. Kucharenko, I.N. Iakovenko, S.M. Yarmoluk, V.S. Brovarets. Ukrainica Bioorganica Acta. – 2008. – V. 6, № 1. – P. 28-36. 
  17. The role of protein kinase CK2 in the regulation of oncogenesis, apoptosis and cellular stress response. G.P. Volynets, A.G. Golub, V.G. Bdzhola, S.M. Yarmoluk. Ukrainica Bioorganica Acta. – 2007. – V. 5, № 2. – P. 25-32. 
  18. Kirchhoff atomic charges fitted to multipole moments: Implementation for a virtual screening system. O. Yakovenko, A. Оliferenko, V. Bdzhola, V. Palyulin, N. Zefirov. Journal of Computational Chemistry. – 2008. – 29. – P. 1332-1343. 
  19. The new method of distribution integrals evaluations for high throughput virtual screening. O.Ya. Yakovenko, A.A. Oliferenko, A.G. Golub, V.G. Bdzhola, S.M. Yarmoluk. Ukrainica Bioorganica Acta. – 2007. – V. 5, № 1. – P. 52-62. 
  20. Application of distribution function of rotation and translation degrees of freedom for CK2 inhibitors Ki estimation. O.Ya. Yakovenko, A.G. Golub, V.G. Bdzhola, S.M.Yarmoluk. Ukrainica Bioorganica Acta. – 2006. – V. 4, № 2. – P. 47-55
  21. Evaluation of 3-Carboxy-4(1H)-quinolones as Inhibitors of Human Protein Kinase CK2. Golub AG, Yakovenko OY, Bdzhola VG, Sapelkin VM, Zien P, Yarmoluk SM.  J Med Chem. 2006; 49(22), 6443-50.
  22. Evaluation of 4H-4-chromenone derivatives as inhibitors of protein kinase CK2., A. O. Prykhod’ko, O. Ya. Yakovenko, A. G. Golub, A. G. Bdzhola, S. M. Yarmoluk, Biopolymers and cell. – 2005. – V. 21, 3. – P. 287–292.
  23. Search for protein kinase CK2 inhibitors among 3-carboxy-4-aminoquinoline derivatives., V. M. Sapelkin, A. G. Golub, O. Ya. Yakovenko, V. G. Bdzhola, S. M. Yarmoluk, Ukrainica Bioorganica Acta. – 2005. – V. 1, 1. – P. 28–32.
  24. Search for casein kinase 2 inhibitors among 4 aminoquinazoline derivatives., V. M. Sapelkin, A. G. Golub, O. Ya. Yakovenko, V. G. Bdzhola, S. M. Yarmoluk, Ukrainica Bioorganica Acta. – 2004. – V. 1, 1–2. – P. 74–79.
  25. Inhibitors of protein kinase CK2., A. O. Prykhod'ko, G. G. Dubinina, S. M. Golovach, S. M. Yarmoluk, Ukrainica Bioorganica Acta. – 2004. – V. 1, 1–2. – P. 39–48.
  26. Synthesis of (1,1-dioxido-3-oxoisothiazolidin-2-yl)-benzenesulfonamides. M.O.Chekanov, А.R.Synyugin, S.S.Lukashov, S.M. Yarmoluk. Ukrainica Bioorganica Acta. – 2008. – V. 6, № 1. – P. 55-60.
  27. Synthesis and structural study of N-substituted-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxides. P.V. Shaitanov, S.S. Lukashov, O.V. Turov, S.M. Yarmoluk. Ukrainica Bioorganica Acta. – 2007. – V. 5, № 2. – P. 56-61.
  28. Synthesis of 4-substituted 1-arylhexahydrothieno[3,4-b]pyrazin-2(1H)-one 6,6-dioxides. P.V. Shaitanov, Yu.V. Bezugly, V.M. Sapelkin, S.M. Yarmoluk. Ukrainica Bioorganica Acta. – 2006. – V. 4, № 2. – P. 40-46.
  29. Synthesis and structural characteristics of 4-(2-phenylethyl)-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxide. P.V. Shaitanov, Yu.V. Bezugly, V.M. Charchenko, S.M. Lukashov, S.M. Yarmoluk. Ukrainica Bioorganica Acta. – 2005. – V.3, № 2. – P. 39-42.
  30. Synthesis of 7-(3-dialkylamino-2-hydroxypropoxy)-3-aryloxychromones. A. O. Prykhodko, S. P. Kobzev, S. M. Yarmoluk. Ukrainica Bioorganica Acta. – 2005. – V. 2, № 1. – P. 33-39.
  31. Synthesis of 7-(3-dialkylamino-2-hydroxypropoxy)-3-aryloxychromones., A. O. Prykhodko, S. P. Kobzev, S. M. Yarmoluk, Ukrainica Bioorganica Acta. – 2005. – V. 1, 1. – P. 33–39 (in Ukrainian).
  32. Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluorometthyl-4H-4-chromenone derivatives against 60 human cancer cell lines., Prykhod’ko A.O., Dubinina G.G., Khilya V.P., Yarmoluk S.M., Biopolymers and cell. – 2004. – V. 20, 1–2. – P. 159–163 (in Ukrainian).
  33. Interaction of 7-R-3-R1-7,8-dihydro-2Н,6Н-pyrrolo[3',4':4,5][1,3]thiazolo[3,2-b][1,2,4]triazine-2,6,8-triones with N-nucleophiles., G. G. Dubinina, S. M. Golovach, S. S. Tarnavsky and S. M. Yarmoluk, Ukr. Khim. Zh. - 2003. - V. 69, ¹ 4. - p. 35-39 (in Ukrainian).
  34. Synthesis of potential biologically active substances on the base of 5-carboxymethylidene-2,4-thiazolidinedione., R.B. Lesyk, B.S. Zimenkovsky, S.M. Yarmoluk, I.Yu. Subtel’na, Pharmaceutical journal. – 2003. – ¹ 1. – P. 51–56 (in Ukraine).
  35. The relationship of antitumor activity with the structure of 3-chloro-4-(3-hydroxyanilino)-2,5-dihydropyrrole-2,5-diones., S. S. Tarnavsky, G. G. Dubinina, S. M. Golovach and S. M. Yarmoluk, Biopolymers and Cell. - 2003. - V.19, N 6. - P. 548-552 (in Ukrainian)
  36. The search of antitumor activity among derivatives of the 2,5-dihydropyrrole-2,5-dione., S. S. Tarnavsky, G. G. Dubinina, S. M. Golovach and S. M. Yarmoluk, Biopolymers and Cell. - 2003. - V.19, N 3. - P. 287-291 (in Ukrainian)
  37. Antitumor activity of the 6-substituted derivatives of the 4-alkylaminoquinazolines., V. M. Sapelkin, I. E. Ìàkovenko, S. S. Lukashov, G.G. Dubinina and S. M. Yarmoluk, Biopolymers and Cell. - 2003. - V.19, N 5. - P. 467-472 (in Ukrainian)
  38. Inhibitors of cyclin-dependent kinases. I. Synthesis of combinatorial libraries of 8-aminomethyl derivatives of 3-aryloxy-7-hydroxychromones and study of their antitumor activity., V. V. Arkhipov, A. O. Prykhod'ko, A. G. Golub, V. P. Khilya and S. M. Yarmoluk, Biopolymers and Cell. - 2003. - V.19, N 2. - P. 196-201 (in Ukrainian)
  39. Interaction of 3,4-dichloromaleimides with N- and S-nucleophiles., G. G. Dubinina, S. S. Tarnavsky, S. M. Golovach and S. M. Yarmoluk, Ukr. Khim. Zh. - 2002. - V. 68, ¹ 8. - p. 47-51 (in Ukrainian).
  40. Reaction of N-substituted 3,4-dichloromaleimides with a-mercaptoazaheterocycles., G. G. Dubinina, Yu. M. Volovenko, S. M. Yarmoluk, S. V. Shishkina, O. V. Shishkin, Heterocycles. - 2001. - N 11. - P. 2189-2198
  41. The N4-aminoacid derivatives of 6-azacytidine: Syntheses and biological activity., I.V. Alekseeva, L.I. Palchikovska, A.S. Shalamay, S.S. Tarnavsky, L.N. Nosach, N.S. Dyachenko, Biopolymers and Cell. - 1997. - V.13, N 4. - P. 285-290 (in Russian).