Department of Medicinal Chemistry


Sergiy M. Yarmoluk

Professor, Dr. Sci. (Chem.)
Phone: (380-44) 522–24–58;
Fax: (380-44) 522–24–58.

Education and Degrees:

Graduate Student, Taras Shevchenko National University of Kyiv, M.Sc. (chemistry of organic compounds)

1985–1989 Postgraduate Student, Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia

1989 Ph.D. (ñhemistry)

2005 Dr.Sci. (chemistry), Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

2006 Professor (bioorganic chemistry)

Professional Employment:

1979–1983 Engineer, IMBG NASU

1983–1984 Senior Engineer, IMBG NASU

1984–1985 Senior Engineer, Institute of Bioorganic Chemistry, NASU, Kyiv, Ukraine

1985–1987 Senior Engineer, IMBG NASU

1987–1993 Junior Research Scientist, IMBG NASU

1993–1995 Research Scientist, IMBG NASU

1995–2002 Senior Research Scientist, IMBG NASU

2002–2003 Leading Research Scientist, IMBG NASU

Since 2003 Head of the Department of Medicinal Chemistry, IMBG NASU


Since 2004 Deputy Editor of Journal “Ukrainica Bioorganica Acta” (Ukraine)

Editorial Board member of Journal “Biopolymers and Cell” (Ukraine)

Since 2008 Editorial Board member of Journal “Biotechnic and Histochemistry” (Sweden)

Honours, Prizes, Awards:

2003 Diploma of Honour and valuable gift from Mayor of Kyiv

2005 Diploma of Honour from the Ministry of Education and Science of Ukraine

2012 National Prize of Autonomous Republic of Crimea

Research Area:

Computer-aided drug design

Development of fluorescent probes for protein and nucleic acid detection

Ñurrent Research Activities and Recent Achievements:

Development of low-molecular inhibitors of protein kinase CK2.

In order to discover enzyme inhibitors we have performed screening program, using both in silico and in vitro approaches. AutoDock and DOCK software were used to conduct receptor-ligand flexible docking. The virtual screening experiments were carried out targeting the ATP binding site of protein kinase by searching compound library of about 100,000 compounds. Several hundreds ligands have been selected and taken for the kinase assay study. In vitro experiments allowed us to identify a number of novel classes of CK2 inhibitors – derivatives of (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acid, 3-carboxyquinoline and 4,5,6,7-tetrahalogeno-1,3-isoindolinedione. Guided by both molecular modeling and SAR analysis chemical optimization of the identified hit compounds allowed us significantly improve their activity and obtain nanomolar and selective CK2 inhibitors. The most active compound inhibiting CK2 belongs to flavonols (IC50=9 nM). This inhibitor was called FLC21 (Fig. 1).

Fig. 1. Chemical structure of the inhibitor FLC21 and its binding mode with the active site of protein kinase CK2
In silico design of ASK1 inhibitors.

We have identified and characterized two classes of ASK1 inhibitors – 3H-naphtho[1,2,3-de]quinoline-2,7-diones and 2-thioxo-thiazolidin-4-ones. Structure-activity relationships of their derivatives have been studied and binding modes of these chemical classes have been predicted. The most perspective inhibitors were called NQDI-1 (IC50=3 μM) and PFTA-1 (IC50=650 nM) (Fig. 2). In our preliminary selectivity studies these compounds exhibited specific inhibitory activity towards ASK1. Compounds NQDI-1 and PFTA-1 demonstrated some cytoprotective effect in HEK293 during apoptosis induced by CHI3L2.

Fig. 2. Chemical structure of the inhibitor PFTA-1 and its binding mode with the active site of protein kinase ASK1
The search for inhibitors of protein kinase FGFR1.

Using virtual screening experiments and in vitro tests we have found several classes of FGFR1 inhibitors: flavones, phenylbenzisoxazoles and aminopyrimidines. Then, we have performed ligand-oriented virtual screening and identified highly active inhibitors from the classes of oxindoles and quinazolines.

The development of new, efficient methods in the field of receptor-oriented high-throughput virtual screening.

We have discovered and parameterized novel method for generating inexpensive and electrostatically reasonable atomic charges of organic compounds. This method is based on the principle of electronegativity relaxation of the Kirchhoff charge model. The new Kirchhoff charges were implemented into a virtual screening engine. To increase accuracy of ligand-receptor interaction energy evaluation the Kirchhoff charges calculation model was used for creating a new force field YFF. This force field is obtained by joining Van-der-Waals and bonded part of well-known MMFF94 with our charge calculation scheme.

Design of fluorescent probes for biomedical applications.

We proposed cyanine dyes for detection of protein aggregation and for studies of globular protein conformational changes. Squaraine dyes have been proposed as efficient noncovalent fluorescent labels for albumins. Series of sensitive fluorescent probes for nonspecific detection of proteins in gels (Lucy506, Lucy569 and Lucy565) were developed by our scientists for Sigma-Aldrich Inc. In collaboration with Sigma-Aldrich we successfully developed novel high-sensitive fluorescent dye Nancy-520 for DNA visualization in gels. The dyes Cyan2 and Cyan40 can provide a highly sensitive method for detection and quantification of non-canonical DNA structures in genome and could be used for the search and development of agents that specifically bind with mentioned DNA motifs and inhibit their functioning (Fig. 3).

Fig. 3. Chemical structures of FGFR1 inhibitors

National Grants:

Projects of National Academy of Sciences of Ukraine

  • 2010–2014 N 30/12 Project: “Development of technologies of target-oriented search for inhibitors of aminoacyltRNA- synthetases with selective action against causative agents of human infective diseases” (scientific supervisor – Tukalo M. A.)

International Grants:

  • 2011–2013 STCU (Science and Technology Center in Ukraine) N 5508 Project: “Development of macrocyclic metallocomplexes – inhibitors of formation of amyloid fibril in neurodegenerative diseases” (scientific supervisor – Yarmoluk S. M.)
  • 2010–2012 STCU N 5218 Project: “Rational search for inhibitors of aminoacyl-tRNA-synthetases with selective action against causative agent of tuberculosis” (scientific supervisor – Tukalo M. A.)
  • 2011–2012 STCU N 5281 Project: “Development of fluorescent dyes for detection of oligomeric amyloid intermediates in neurodegenerative diseases” (scientific supervisor – Yarmoluk S. M.)


with Ukrainian organizations:

  • Institute of Organic Chemistry, NASU, Colour and Structure of Organic Compounds Department (Kyiv)
  • Institute of Bioorganic Chemistry and Petrochemistry, NASU (Êyiv)
  • Institute for Scintillation Materials, NASU (Kharkiv)
  • Vernadsky Institute of General and Inorganic Chemistry, NASU (Kyiv)

with foreign organizations:

  • University Trás-os-Montes and Alto Douro (Vila Real, Portugal)
  • University of Twente, Biophysical Engineering Group (Enschede, Netherlands)
  • University of Southern Denmark (Denmark)
  • University of Cologne (Cologne, Germany)
  • Institute of Clinical Pharmacology, Hannover Medical School (Hannover, Germany)

Selected publications:

  1. J. Blechinger, O.A. Varzackii, V. Kovalska, G.E. Zelinskii, Y.Z. Voloshin, E. Kinski, A. Mokhir. Cytotoxicity of electrophilic iron(II)-clathrochelates in human promyelocytic leukemia cell line. Bioorganic and Medicinal Chemistry Letters. 2016, 26: 626-629.
  2. G.P. Volynets, O.B. Gorbatiuk, O.P. Kukharenko, M.O. Usenko, S.M. Yarmoluk. Production of recombinant human apoptosis signal-regulating kinase 1 (ASK1) in Escherichia coli. Protein Expression and Purification. 2016, 126: 89-92.
  3. A.R. Syniugin, M.O. Chekanov, P.V. Savitskiy, A.E. Pashenko, T.S. Zhuk, S.M. Yarmoluk, A.A. Fokin. New method for the synthesis of pyrrolo[2,3-b]dihydroquinolines. Tetrahedron Letters. 2016, 57: 213-215.
  4. V. Kovalska, S. Chernii, M. Losytskyy, Y. Dovbii, I. Tretyakova, R. Czerwieniec, V. Chernii, S. Yarmoluk, S. Volkov. β-ketoenole dyes: synthesis and study as fluorescent sensors for protein amyloid aggregates. Dyes and Pigments. 2016, 132: 274-281.
  5. A.A. Gryshchenko, S.S. Tarnavskiy, K.V. Levchenko, V.G. Bdzhola, G.P. Volynets, A.G. Golub, T.P. Ruban, K.V. Vygranenko, L.L. Lukash, S.M. Yarmoluk. Design, synthesis and biological evaluation of 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones as inhibitors of protein kinase FGFR1. Bioorganic and Medicinal Chemistry. 2016, 24: 2053-2059.
  6. O.V. Ostrynska, A.O. Balanda, V.G. Bdzhola, A.G. Golub, I.M. Kotey, O.P. Kukharenko, A.A. Gryshchenko, N.V. Briukhovetska, S.M. Yarmoluk. Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines. European Journal of Medicinal Chemistry. 2016, 115: 148-160.
  7. Starosyla S, Volynets G, Lukashov S, Gorbatiuk O, Golub A, Bdzhola V, Yarmoluk S. Identification of Apoptosis signal-regulating kinase 1 (ASK1) inhibitors among the derivatives of Benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one. Bioorganic and Medicinal Chemistry. 2015;23:2489-2497.
  8. Chernyshenko O, Chernyshenko T, Korolova D, Volynets all. Non-enzymatic activation of prothrombin induced by interaction with fibrin β26-42 region. Acta Biochimica Polonica. 2015;62(3):517-522.
  9. Guerra B, Bischoff N, Bdzhola V... at all. A note of caution on the role of halogen bonds for protein kinase/inhibitor recognition suggested by high- and low-salt CK2α complex structures. ACS Chem. Biol. 2015;10:1654-1660.
  10. Gryshchenko A, Bdzhola V, Balanda A... at all. Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1. Bioorg. Med. Chem. 2015;23(9)2287-2293.
  11. Kuperman M, Chernii S, Losytskyy M,...Yarmoluk S. Trimethine cyanine dyes as fluorescent probes for amyloid fibrils: The effect of N,N’-substituents. Analytical Biochemistry. 2015;484:9-17.
  12. Repich H, Orysyk S, Bon V... Pekhnyo V. Mono- and binuclear Pd(II) complexes with 2-(5,6-di¬methyl-4-oxo-3,4-dihydro¬thieno[2,3-d]pyrimidin-2-yl)-N-phenylhydrazine¬carbothio¬amide: Synthesis, crystal structure and spectroscopic characterization. Journal of Molecular Structure. 2015;1102:161-169.
  13. Starosyla SA, Volynets GP, Bdzhola VG, et al. ASK1 pharmacophore model derived from diverse classes of inhibitors. Bioorganic and Medicinal Chemistry Letters. 2014;24:4418-4423.
  14. Chekanov MO, Ostrynska OV, Synyugin AR, et al. Design, synthesis and evaluation of 2-phenyli-sothiazolidin-3-one-1,1- dioxides as a new class of human protein kinase CK2 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2014;29(3):338-343.
  15. Chekanov MO, Ostrynska OV, Tarnavskyi SS, et al. Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6-aza-analogs as a new class of CK2 inhibitors. J Enzyme Inhib Med Chem. 2014;29(5):639-46.
  16. Kovalska VB, Losytskyy MY, Reis LV, et al. Fluorescent detection of a partially unfolded conformation of beta-lactoglobulin using squaraine dyes. Macromolecular Symposia. 2014;335(1):43-50.
  17. Inshyn DI,Kovalska VB, Losytskyy MY, et al. Development of a quantitative structure activity relations (QSAR) model to guide the design of fluorescent dyes for detecting amyloid fibrils. Biotechnic and Histochemistry. 2014;89(1):1-7.
  18. Kovalska VB, Losytskyy MY, Varzatskii OA, et al. Study of anti-fibrillogenic activity of iron(II) clathrochelates. Bioorganic and Medicinal Chemistry. 2014;22(6):1883-1888.
  19. Severinovskaya OV, Kovalska VB, Losytskyy MY, et al. Application of MALDI-TOF mass spectrometry for study on fibrillar and oligomeric aggregates of alpha-synuclein. Biopolym. Cell. 2014;30(3):190-196.
  20. Kovalska VB, Losytskyy MY, Chernii SV, et al. Towards the anti-fibrillogenic activity of phthalocyanines with out-of-plane ligands: correlation with self-association proneness. Biopolymers and Cell. 2013;29(6):473-479.
  21. Yarmoluk S. M., Nyporko A. Yu., Bdzhola V. G. Rational design of protein kinase inhibitors Biopolym. Cell. 2013; 29(4):339-347 doi:10.7124/bc.000828
  22. Volynets G, Bdzhola V, Golub A, et al. Rational design of apoptosis signalregulating kinase 1 inhibitors: discovering novel structural scaffold. Eur J Med Chem. 2013; 61:104–115. doi:10.1016/j.ejmech.2012.09.022
  23. Kovalska V, Losytskyy M, Chernii V, et al. Studies of antifibrillogenic activity of phthalocyanines of zirconium containing out of plane ligands. Bioorg Med Chem. 2012; 20(1):330–4. doi: 10.1016/j.bmc.2011.10.083
  24. Kovalska VB, Losytskyy MY, Tolmachev OI, et al. Tri- and pentamethine cyanine dyes for fluorescent detection of ?¬synuclein oligomeric aggregates. J Fluoresc. 2012; 22(6):1441–8. doi:10.1007/s10895-012-1081-x
  25. Yakovenko OY, Li YY, Oliferenko AA, Vashchenko GM, Bdzhola VG, Jones SJ. Ab initio parameterization of YFF1, a universal force field for drug-design applications. J Mol Model. 2012;18(2):663–73. doi:10.1007/s00894-011-1095-3
  26. Golub AG, Gurukumar KR, Basu A, et al. Discovery of new scaffolds for rational design of HCV NS5B polymerase inhibitors. Eur J Med Chem. 2012;58:258–64. doi:10.1016/j.ejmech.2012.09.010
  27. Volynets GP, Chekanov MO, Synyugin AR, et al. Identification of 3H-naphtho[1,2,3-de]quinoline-2,7-diones as inhibitors of apoptosis signal-regulating kinase 1 (ASK1). J Med Chem. 2011;54(8):2680–6. doi:10.1021/jm200117h
  28. Golub AG, Bdzhola VG, Briukhovetska NV, et al. Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2. Eur J Med Chem. 2011;46(3):870–6. doi:10.1016/j.ejmech.2010.12.025
  29. Kramerov AA, Golub AG, Bdzhola VG, et al. Treatment of cultured human astrocytes and vascular endothelial cells with protein kinase CK2 inhibitors induces early changes in cell shape and cytoskeleton. Mol Cell Biochem. 2011;349(1–2):125–37. doi: 10.1007/s11010-010-0667-3
  30. Volkova KD, Kovalska VB, Losytskyy MYu, et al. Aza-substituted squaraines for the fluorescent detection of albumine. Dyes Pigments. 2011; 90(1):41–7. doi: 10.1016/j.dyepig.2010.11.005