Werner Tjarks PhD

Werner Tjarks PhD
Assoc ProfessorCollege of Pharmacytjarks.1@osu.edu
430 Parks Hall 500 W 12th Avenue Columbus Ohio 43210
Phone:614-292-7624Fax: 614-292-2435
  • Experimental Therapeutics

General Research Interest

Nucleosides for anticancer, antiviral, and antibiotic therapies.

Research Description

Nucleoside antimetabolites such as gemcitabine, cytarabine, cladribine, fludarabine, clofarabine, acyclovir, ganciclovir, brivudine, zidovudine, stavudine, and emtricitabine are prodrugs that are widely used as anticancer agents or antiviral agents and their importance continues to increase. These antimetabolites utilize nucleoside salvage pathways for their transformation into active nucleoside triphosphates. Irrespective of the final intracellular targets of the triphosphates, which primarily are human or viral DNA and their respective polymerases or reverse transcriptases, the rate-limiting key activation step of the prodrugs is usually the initial conversion of the nucleoside to the corresponding monophosphate by phosphorylating enzymes, often deoxynucleoside kinases. Thymidine kinase (TK) is one of these deoxynucleoside kinases. Most eukaryotes and prokaryotes and many DNA viruses code for proteins with thymidine kinase activity. However, among all approved nucleoside antimetabolites only the HIV prodrugs zidovudine and stavudine are activated by human thymidine kinase 1 (hTK1). This is probably due to the fact that TKs have the most stringent substrate specificity among all nucleoside kinases and that crystal structures for drug design have only become available very recently. Dr. Tjarks’ research activities focus on the in silico design, synthesis, and biological evaluation of inhibitors and substrates of TKs from e.g. Bacillus anthracis and Epstein-Barr virus as well as from hTK1 for antibiotic, antiviral, and anticancer therapies.

Transinstitutional Work

Staffan Eriksson, M.D. , Ph.D., Swedish University of Agricultural Sciences, evaluation of boronated nucleosides for boron neutron capture therapy. Rolf F. Barth, M.D., OSU Department of Pathology, evaluation of boronated nucleosides for boron neutron capture therapy.

Current Publications

  • Sjuvarsson E, Damaraju VL, Mowles D, Sawyer MB, Tiwari R, Agarwal HK, Khalil A, Hasabelnaby S, Goudah A, Nakkula RJ, Barth RF, Cass CE, Eriksson S, Tjarks WCellular influx, efflux, and anabolism of 3-carboranyl thymidine analogs: potential boron delivery agents for neutron capture therapy.J Pharmacol Exp Ther 347 388-97 11/1/2013
  • Khalil A, Ishita K, Ali T, Tjarks WN3-substituted thymidine bioconjugates for cancer therapy and imaging.Future Med Chem 5(6) 677-92 4/1/2013
  • Agarwal HK, McElroy CA, Sjuvarsson E, Eriksson S, Darby MV, Tjarks WSynthesis of N3-substituted carboranyl thymidine bioconjugates and their evaluation as substrates of recombinant human thymidine kinase 1.Eur J Med Chem 60 456-68 2/1/2013
  • Hasabelnaby S, Goudah A, Agarwal HK, Abd Alla MS, Tjarks WSynthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors.Eur J Med Chem 55 325-34 9/1/2012

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) 300 W. 10th Ave. Columbus, OH 43210 Phone: 1-800-293-5066 | Email: jamesline@osumc.edu