James W. Janetka

James W. Janetka, Ph.D.

Associate Professor
Biochemistry and Molecular Biophysics
Lab Website
Publications (link to PubMed Central)
 

 
 

 

Office: 2614 Cancer Research
Phone: 314-362-0509
Email: janetkaj at biochem.wustl.edu

Research

My research group is interested in the rational X-ray structure-based drug design (SBDD) and synthesis of non-traditional peptide-based and small molecule antagonists of proteases in cancer, lectins in bacterial pathogenesis, and protein-protein interactions (PPIs) important in DNA-damage repair pathways. These chemical biology tools are utilized for studying the molecular recognition and regulation of protein ligands and pathogenic mechanisms of disease. My group has extensive experience and expertise in organic synthesis and drug discovery. The initial tool compounds are identified either by using natural protein substrates and ligands or by high-throughput screening (HTS). These hits serve as lead molecules for further medicinal chemistry optimization using SBDD to develop activity-based biological probes and potential therapeutics for the treatment of metastatic cancer and resistant bacterial infections.

JanetkaLab Graphic

Most Recent Publications

  • Han, Z., Harris, P.K.W., Jones, D.E., Chugani, R., Kim, T., Agarwal, M., Shen, W., Wildman, S.A. and Janetka, J.W. Inhibitors of HGFA, matriptase and hepsin serine proteases: A non-kinase strategy to block cell signaling in cancer. ACS Med. Chem. Lett. (E-pub ahead of print.) (2014). [Abstract]
  • Totsika, M., Kostakioti, M., Hannan, T.J., Upton, M., Beaton, S.A., Janetka, J.W., Hultgren, S.J. and Schembri, M.A. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug resistant uropathogenic Escherichia coli ST131. J Infec Dis 208:921-928 (2013). [Abstract]

  • Guiton, P.S., Cusumano, C.K., Kline, K.A., Dodson, D.W., Han, Z., Janetka, J.W., Henderson, J.P., Caparon, M.G. and Hultgren, S.J. Combination small molecular therapy prevents uropathogenic Escherichia coli cather-associated urinary tract infections in mice. Antimicrob Agents Chemother. 56:4738-4745 (2012). [Abstract]

  • Kostakioti, M., Hadjifrangiskou, M., Cusumano, C.K., Hannan, T.J., Janetka, J.W. and Hultgren, S.J. Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection. Infect Immun 80:2826-2834 (2012). [Abstract]
  • 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. 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 55:5130-5142 (2012). [Abstract]
  • Yang, B., Hird, A.W., Russell, D.J., Fauber, B.P., Dakin, L.A., Zheng, X., Su, Q., Godin, R., Brassil, P., Devereaux, E. and Janetka, J.W. Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO. Bioorganic & Medicinal Chemistry Letters 22:4907-4911 (2012). [Abstract]
  • Han, Z., Pinkner, J.S., Ford, B., Chorell, E., Crowley, J.M., Cusumano, C.K., Campbell, S., Henderson, J.P., Hultgren, S.J. and Janetka, J.W. Lead optimization studies on FimH antagonists: Discovery of potent and orally bioavailable ortho-substituted biphenyl mannosides. Journal of Medicinal Chemistry 55:3945-3959 (2012). [Abstract]
  • Cusumano, C.K., Pinkner, J.S., Han, Z., Greene, S.E., Ford, B.A., Crowley, J.R., Henderson, J.P., Janetka, J.W. and Hultgren, S.J. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Science Translational Medicine 3:1-10 (2011). [Abstract]
  • Ma, C.X., Janetka, J.W. and Piwnica-Worms, H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends in Molecular Medicine 17:88-96 (2011). [Abstract]
  • Oza, V., Ashwell, S., Brassil, P., Breed, J., Deng, C., Ezhuthachan, J., Haye, H., Horn, C., Janetka, J., Lyne, P., Newcombe, N., Otterbien, L., Pass, M., Read, J., Roswell, S., Su, M. Toader, D., u, D., Yu, Y., Valentine, A., Webborn, P., White, A., Zabludoff, S. and Zheng, X. Discovery of a novel class of triazolones as checkpoint kinase inhibitors – Hit to lead exploration. Bioorganic & Medicinal Chemistry Letters 20:5133-5138 (2010). [Abstract]
  • Han, Z., Pinkner, J.S., Ford, B., Obermann, R., Nolan, W., Wildman, S.A., Hobbs, D., Ellenberger, T., Cusumano, C.K., Hultgren, S.J. and Janetka, J.W. Structure-based drug design and optimization of mannoside bacterial FimH antagonists. J Med Chem 53:4779-4792 (2010). [Abstract]
  • Aronov, A.A., Tang, Q., Martinez-Botella,G., Bemis, G.W., Cao, J., Chen, G., 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. and Xie, X. Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J Medicinal Chemistry 52:6362-6368 (2009). [Abstract]
  • Janetka, J.W., Almeida, L., Ashwella, S., Brassil, P.J., Daly, K., Deng C., Gero, T., Glynn, R.E., Horn, C.L., Ioannidis, S., Lyne, P., Newcombe, N.J., Oza, V.B., Pass, M., Springer, S.K., Su, M., Toader, D., Vasbinder, M.M., Yu, D., Yu, Y. and Zabludoff, S.D. Discovery of a novel class of 2-ureido thiophene carboxamide checkpoint kinase inhibitors. Bioorganic & Medicinal Chemistry Letters 18:4242-4248 (2008). [Abstract]

  • Zabludoff, S.D., Deng C., Grondine, M.R., Sheehy, A.M., Ashwell, S., Cale, B.L., Green, S., Haye, H.R., Horn, C.L., Janetka, J.W., Liu, D., Mouchet, E., Ready, S., Rosenthal, J.L., Queva, C., Schwartz, G.K., Taylor, K.J., Tse, A.N., Walker, G.E., and White, A.M. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Molecular Cancer Therapeutics 7:2955-2966 (2008). [Abstract]
  • Kim, I.J., Ullrich, T., Janetka, J.W., Coop, A., Furness, M.S., Jacobson, A.E., Rothman, R.B., Baumann, M.H., Dersch, C.M., Flippen-Anderson, J.L., George, C. and Rice, K.C. Diaryldimethylpiperazine ligands with μ- and σ-opioid receptor affinity. Synthesis of (+)-4-[(αR)-α-(4-Allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide and (-)-4-[(αR)-α-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide. Bioorganic and Medicinal Chemistry 11:4761-4768 (2003). [Abstract]
  • Janetka, J.W., Raman, P., Satyshur, K.A., Flentke, G.R. and Rich, D.H. Novel cyclic biphenyl ether peptide Β-strand mimetics and HIV-protease inhibitors. J Am Chem Soc 119:441-442 (1997). [Abstract]