James Janetka

Associate Professor of Biochemistry and Molecular Biophysics (School of Medicine)
Affiliated Professor of Chemistry
PhD Organic Chemistry, University of Wisconsin-Madison
research interests:
  • Organic Chemistry
  • Biological Chemistry
  • Organic Synthesis
  • Drug Discovery
  • Structure-Based Design
  • Cancer
  • Infectious Disease
  • Metastasis
  • Cell-Signaling
  • Synthesis
  • Medicinal Chemistry
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    • 8231 (Medical School Campus)
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    The Janetka research group is studying therapeutic targets and cellular mechanisms in cancer and infectious disease. The overall focus of the lab is to interfere with key biological processes outside the cell, by inhibiting one or more key proteins, which are important in bacterial pathogenesis or tumor progression. We employ rational structure-based drug design and synthetic medicinal chemistry to develop peptide-based and small molecule inhibitors as chemical tools to help decipher mechanisms of disease. In one project we are developing glycoside-based antagonists of adhesins, such as FimH, FmlD, and PapG, in E. coli., which are essential for host-bacteria interactions in UTI. In another project, we are developing peptide-based and small molecule inhibitors of serine proteases, including HGFA, matriptase and hepsin, which post-translationally process the growth factor ligands of c-MET and RON receptor tyrosine kinases, both important in tumor progression and metastatic cancer. The long-term goal of our research is to identify preclinical candidate drugs as new and innovative medicines for treating patients with resistant infections and cancer.

    Selected Publications

    Totsika, M., Kostakioti, M., Hannan, T. J., Upton, M., Beatson, S. A., Janetka, J. W., Hultgren, S. J., and Schembri, M. A. (2013). A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug resistant uropathogenic Escherichia coli ST131, Journal of Infectious Diseases, 208(6), 921-8. PMID: 23737602.

    Han, Z.; Pinkner, J.S.; Ford, B.; Chorell, E.; Crowley, J.M.; Cusumano, C.K.; Campbell, S.; Henderson, J.P.; Hultgren, S.J.; Janetka, J.W. (2012). Lead Optimization Studies on FimH Antagonists: Discovery of Potent and Orally Bioavailable Ortho-Substituted Biphenyl Mannosides. Journal of Medicinal Chemistry, 55, 3945–3959. PMID: 22449031.

    Oza, V.B., Ashwell, S., Almeida, L., Brassil, P., Bree, J., Deng, C., Gero, T., Grondine, M., Horn, C., Ioannidis, S., Liu, D., Lyne, P.D., Newcombe, N., Pass, M., Read, J., Ready, S., Rowsell, S., Su, M., Toader, D., Vasbinder, M., Yu, D., Yu, Y., Xue, Y., Zabludoff, S. and Janetka, J.W. (2012). Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure based design and optimization of thiophene carboxamide ureas. Journal of Medicinal Chemistry, 55(11), 5130–5142.

    Yang, B., Hird, A. W., Russell, D. J., Fauber, B. P., Dakin, L. A., Zheng, X. L., Su, Q. B., Godin, R., Brassil, P., Devereaux, E., and Janetka, J. W. (2012) Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO, Bioorg. Med. Chem. Lett. 22, 4907-4911.

    Cusumano, C.K., Pinkner, J.S., Han, Z., Greene, S., Ford, B., Janetka, J.W., Hultgren, S.J. (2011). Treatment and Prevention of Urinary Tract Infection with Orally Active Mannoside FimH Inhibitors. Science Translational Medicine, 3, 109, 1-10. PMID: 22089451.

    Han, Z.; Pinkner, J.S.; Ford, B.; Obermann, R.; Nolan, W.; Wildman, S.A.; Hobbs, D.; Ellenberger, T.; Cusumano, C.K.; Hultgren, S.J.; Janetka, J.W. (2010). Structure-Based Drug Design and Optimization of Mannoside Bacterial FimH Antagonists Journal of Medicinal Chemistry, 53, 4779-479. PMID: 20507142.

    Aronov, A. M.; Tang, Q.; Martinez-Botella, G.; Bemis, G. W.; Cao, J. R.; Chen, G. J.; Ewing, N. P.; Ford, P. J.; Germann, U. A.; Green, J.; Hale, M. R.; Jacobs, M.; Janetka, J. W.; Maltais, F.; Markland, W.; Namchuk, M. N.; Nanthakumar, S.; Poondru, S.; Straub, J.; ter Haar, E.; Xie, X. L. (2009). Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry, 52, 6362-6368.

    Zabludoff, S. D.; Deng, C.; Grondine, M. R.; Sheehy, A. M.; Ashwell, S.; Caleb, B. L.; Green, S.; Haye, H. R.; Horn, C. L.; Janetka, J. W.; Liu, D. F.; Mouchet, E.; Ready, S.; Rosenthal, J. L.; Queva, C.; Schwartz, G. K.; Taylor, K. J.; Tse, A. N.; Walker, G. E.; White, A. M. (2008). AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Molecular Cancer Therapeutics, 7, 2955-2966.

    James W. Janetka, M. Scott Furness, Xiaoyan Zhang, Andrew Coop, John E. Folk, Mariena V. Mattson, Arthur E. Jacobson, and Kenner C. Rice. Enantioconvergent Synthesis of (-)-(2R, 5S)-1-Allyl-2, 5-dimethylpiperazine, an Intermediate to δ-Opioid Receptor Ligands (2003).  J. Org. Chem, 68(10), 3976-3980.

    James W. Janetka, Prakash Raman, Ken A. Satyshur, George R. Flentke, and Daniel H. Rich. Novel Cyclic Biphenyl Ether Peptide β-Strand Mimetics and HIV-Protease Inhibitors (1997). J. Am. Chem. Soc., 119, 441-442.