Regina ZHUK
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Professor Regina ZHUK
Department Director,
Rimonyx Pharmaceuticals, Ltd.
Kiryat Weizmann Science ParkNess-Ziona 70400
P.O.Box 4056
Israel
Home:
Hatayasim 14/11
Nes Ziona 74062
Israel
Phone: +972-89389505
E-mail: reginazhuka@gmail.com
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Born: December 6, 1936, Moscow, Russia
Interests:
- Synthesis of Nucleoside Analogues
- Anticancer, Antiviral and Immunomodulating Drug Design
- Drug Development
Brief Description of Main Research:
Two original drugs designed - anticancer Ftorafur ( Tegafur ) and antiviral Furavir.
Technologies for Ftorafur, Acyclovir and Furavir large scale
production elaborated. A series of 7(9)-substituted guanines is synthesized and
evaluated as immunomodulating agents. A new trend of research is connected
with the investigation of butyric acid derivatives as anti-cancer drugs and
thieno[2,3-c]pyridines as anti-inflammatory agents.
- 125 scientific papers and abstracts published;
- 45 author's certificates and patents granted
- 6 PhD students and 20 Master's degree students supervised
Languages: Russian, Latvian, English
Education:
- Riga Technical University (Faculty of Chemistry), Latvia, 1959
- Dr.chem. (Candidate of Sciences in former USSR, PhD in Western countries), Institute of
Organic Synthesis, Latvian Academy of Sciences, Riga, 1969
- Dr.habil.chem. (Doctor of Sciences in former USSR), Institute of Organic Synthesis,
Latvian Academy of Sciences, Riga, 1977
Thesis:"Analogues of pyrimidine nucleosides and nucleotides"
Experience:
Latvian Institute of Organic
Synthesis:
- Research Associate, Laboratory of the Chemistry of Heterocyclic Compounds, 1965-1969
- Head of Research Group, Laboratory of Nucleic Acids Components, 1969-1994
- Professor of Medicinal Chemistry, 1994 -1999
Bar Ilan University (Israel):
- Professor, 2000 -
- Director Medicinal Chemistry Rimonyx Pharmaceuticals, Ltd., 2003 -
Honours and Awards:
- Foreign Member, Latvian Academy of Sciences, 2000
- Award plague, Taiho Pharmaceutical Company, Tokyo, Japan, 2005
- The D.H.Grindel Medal and Prize (Pharmaceutical Company "Grindex", Latvia),
1995
- Medal and Diploma, Tsurumi University, Yokohama, Japan,1994
- Medal and Diploma, Latvian Institute of Organic Synthesis, 1982
Professional Activities and Memberships:
- President of the Latvian Association for Medicinal Chemistry
- Member of the Management Committee of the European Federation for Medicinal Chemistry
- Member of the International Society of Nucleic Acids Chemistry
- Member of the Editorial Board for The Chinese Pharmaceutical Journal
- Member of the Israel Chemical Society and the Israel Association for Medicinal
Chemistry.
Lectures:
- The lecturer at the 9th International Round Table Nucleosides, Nucleotides
and their Biological Applications, Uppsala, Sweden, 1990, at the XI International
Symposium on Medicinal Chemistry, Jerusalem, Israel, 1990, and
at the 2lst Symposium on Nucleic Acids Chemistry, Matsujama, Japan, 1994.
- Lecture on Drug Design in Nucleoside Analogues. - Institute of Biochemistry,
Martin-Luther University, Halle-Wittenberg, Germany, 1993.
- Lectures on Synthesis of Nucleoside Analogues and Drug Design based on these compounds.
- The National Defense Medical Center, Taipei, Taiwan, Republic of China and National Sun
Yat-Sen University, Kaohsiung, Taiwan, Republic of China, 1994
- Lectures on the Development of the Anticancer Drug Ftorafur. - The Development Center
for Biotechnology, Teipei, Taiwan, Republic of China, 1994; the School of Chemistry,
Kaohsiung Medical College, Kaohsiung, Republic of China, 1994; Tsurumi University,
Yokohama, Okayama University, Okayama, and Taiho Pharmaceutical Co. LTD, Hanno Research
Center, Japan, 1994.
- Lectures on Drug Design in Nucleoside Analogues - Department of Chemistry, Bar
ilan University , Ramat Gan, Israel, 2000; and Department of chemistry, University of
Calgary, Canada, 2001
- Lecture on the History of Ftorafur.-Taiho Pharmaceutical
Co. Hanno Research Center, Japan, 2005
International Collaboration:
- Institute of Biochemistry and Biophysics, PAN, Warsaw, Poland (prof. D.Sugar).
- Martin-Luther University Halle-Wittenburg, Halle, Germany (prof. S.Hoffmann).
- Laboratory of Organic Chemistry, University of Amsterdam, Amsterdam, the Netherlands
(prof. J.G.Koomen).
Recent/Representative Publications:
- S.A.Hiller, R.A.Zhuk, M.Yu.Lidak. Pyrimidine nucleoside analogues. I. N1-(a-furanidyl)derivatives
of natural pyrimidine bases and their antimetabolites. - Dokl. Akad. Nauk SSSR, 1976, N 2,
pp.332-335 (1967) (in Russian).
- S.A.Hiller, R.A.Zhuk, L.A.Sherinya, D.E.Zarin. 1-(a,w-Dihydroxyalkyl)uracils
and their phosphates. - Nucleic Acids Res., Spec., 1975,. Publ. N 1, pp.169-171.
- S.A.Hiller, D.E.Zarin, R.A.Zhuk, Pyrimidine nucleoside analogues X. 5-Substituted
1-(1,3-Dihydroxypropyl-2)uracils. - Nucleic Acids Res., 1976,. 3(3), pp. 721-727.
- R.A.Zhuk, A.E.Berzin, V.N.Silin, E.E.Liepinsh, 2-(5-Substituted uracil-1-yl)
tetrahydrofuran-5-carboxylic acids as pyrimidine ucleotide analogues. - Nucleic Acids
Res., Spec., 1978, Publ. N 3, pp. 19-22.
- Ftorafur. An Antitumor Drug.(Ed. by R.A.Zhuk), 1979, Riga: Zinatne.
- R.A.Zhuk, L.T.Kaulinya, A.S.Ludzisha, E.E.Liepinsh, M.Yu.Lidak. Tetrahydrofuryl- and
alkopxyalkyl analogues of pyrimidine nucleosides. - Nucleic Acids Res., Symp. Ser., 1981,
N 9, pp.123-125.
- A.S.Ludzisha, Je.G.Shpaer, R.A.Zhuk, M.P.Eninsh, N.J.Ghuyeva, Ja.A.Eiduss. Nucleic Acids
Res., Symp. Ser., 1984, N 14, pp. 227-229.
- R.Zhuk, M.Y.Lidak, A.A.Zidermane, A.Gilev. Correlation between structure and activity in
substituted 5-fluorouracils, in Ftorafur, Proceedings of the International Symposium, Ed.
by R.A.Zhuk, 1985, Riga: Zinatne, pp. 16-26.
- M.A.Madre, R.A.Zhuk, M.Y.Lidak. Purine nucleoside analogues. 4. 7-Alkylated
9-(2-hydroxymethyl)guanine. - Chem. Heterocycl. Comp., 1989, vol. 25, N 5, pp. 535-540.
- A.A.Golbraikh, J.Betins, J.Balodis, R.A.Zhuk, G.V.Nikiforovich. Conformational aspects
of antiviral activity of deoxyguanosine acyclic analogues. - Nucleic Acids Res., 1989,
vol. 17, pp. 7965-7977.
- M.Madre, R.Zhuk, M.Lidak. New Prodrugs of Acyclovir with antiviral activity.
-Nucleosides & Nucleotides, 1991, vol.10, pp. 279-282.
- M.A.Madre, R.A.Zhuk, M.Y.Lidak. Purine nucleoside analogues. 5. Acycloguanosine
derivatives, containing O-alkoxyalkyl substituent in the acyclic moiety.- Bioorg. Khim.,
1991, vol. 17, N 11, pp. 1516-1520 (in Russian).
- R.A.Zhuk, M.A.Madre, A.V.Ananiev, L.G.Pogosyan, Zh.J.Akopyan. Antiviral and
immunomodulating activity of acyclic guanosine analogues. - Abstr. of Papers XIIth Intern.
Symp. of Medicinal Chemistry, Basel, Switzerland, Sept. l3-17, 1992, p.333.
- M.A.Madre, R.A.Zhuk, M.Y.Lidak. Purine nucleoside analogues. 6. Chlorination of
acycloguanosine and its derivatives with thionyl chloride. - Chem. Heterocycl. Comp. 1992,
vol. 28, N 5, pp. 567-569.
- R.A.Zhuk, M.A.Madre. Synthesis of 7,8-disubstituted guanines as potential PNP
inhibitors. - Abstr. of Papers 4th Intern. Symp. on Molecular Aspects of Chemotherapy ,
23-25 June 1993, Gdansk-Poland, p.56 (1993).
- R.A.Zhuk, M.A.Madre. Synthesis of 7-(2-hydroxymethyl)guanine and related compounds as
immunomodulators. - Nucleic Acids, Symp. Ser.., 1994, N 31, pp. 5-6.
- M.A.Madre, L.Geita, R.A.Zhuk, G.-J.Koomen. Purine Nucleoside Analogues. 7*.
9-[2-(Alkylthio)ethoxymethyl]Derivatives of Adenine, Hypoxanthine and Guanine. - The
Chinese Pharmaceutical Journal, 1995, vol. 47, pp. 469-481.
- M.A.Madre, R.A.Zhuk, N.Panchenko, J.A.J.Geenevasen, A.M. van den Burg, G.-J.Koomen. Some
peculiarities of N2-acetyl-8-bromoguanine alkylation. - Coll. Czech. Chem. Commun., 1996,
vol. 61, sp. issue, pp. 20-22.
- M.A.Madre, R.A.Zhuk, G.-J.Koomen. Addition of 2,3-dihydrofuran to
N2-acetyl-8-bromoguanine. Nucleosides&Nucleotides., 1997, vol. 6, N
7-9, pp.1107-1110.
- R.A.Zhuk, M.A.Madre, M.Khan, L.Poluektova. Immunosuppressive effects of 8-bromoguanine
derivatives. - 6th Intern. Symp. on Molecular Aspects of Chemotherapy, Gdansk, Poland,
9-12 July 1997: Abstr. book, 1997, p. 135.
- R.A.Zhuk. Structure-activity relationship in ftorafur (tegafur) and related 5-FU
prodrugs, Adv. in experimental medicine and biology. - 1998 - Vol. 431: Purine and
pyrimidine metabolism in man IX, (Ed. A. Griesmacher, P. Chiba, M.M. Muller). - New York:
Plenum Press, 1998, pp. 677-680.
- M.A.Madre, R.A.Zhuk, B.Golankiewicz. Purine nucleoside analogues. 8. N2-Acety-lation
of guanine derivatives. - Polish J. Chem., 1998, vol. 72, N 10, pp. 2242-2246.
- M.A. Madre, R.A. Zhuk, N. Panchenko, J. Geenevasen, A.M. van den Burg, G.-J. Koomen.
Purine nucleoside analogues. 10. A new synthetic route to
8-substituted-7(9)-alkoxyalkylguanines. - Heterocyclic Communications, 1998, vol.
4, N 6, pp.581-588.
- A.Rephaeli, R.Zhuk, A.Nudelman. Prodrugs of butyric acid from bench to bedside:
synthetic design, mechanisms of action, and clinical applications. - Drug Dev. Res.,
2000, vol. 50, pp. 379-391.
- Y.Zimra, A.Nudelman, R.Zhuk, E.Rabizadeh, M.Shaklai, A.Aviram, A.Rephaeli. - J.Cancer
Res. Clin. Oncol., 2000, vol. 126, pp. 693-698.
- A.Nudelman, E.Gnizi, Y.Katz, R.Azulai, M.Cohen-Ohana, R.Zhuk, S.R.Sampson,
L.Langzam, E.Fibach, E.Prus, V.Pugach, A.Rephaeli. Prodrugs of butyric acid. Novel
derivatives possesssing increased aqueous solubility and potential for treating cancer and
blood diseases. - Eur. J. Med., 2001, vol. 36, pp. 63-74.
Patents granted:
- Brit. Pat. 1,168,391 (1969).
- US Pat. 3,635,946 (1972).
- US Pat. 3,912,734 (1975).
- US Pat. 3,947,444 (1976).
- US Pat. 3,954,760 (1976).
- US Pat. 4,916,225 (1990).
Research Projects:
- R.Zhuk (Head of Project). The Development of Antiviral Drugs Acycloguanosine and Furavir
as well as their Delivery Systems. Latvian Council of
Science (1994-1996).
- R.Zhuk (Head of Project). Design of Specific Supramolecular Receptors Based on
Long-alkyl-chain Nucleobase Derivatives. Latvian Council of Science (1997-2000).
- R.Zhuk (Principal Investigator). Synthesis and Biological Properties of Nucleoside
Analogues. NATO International Scientific Exchange Programmes Linkage Grant
(HTECH.LG 940571) (1994)
Last update 05.02 .2008