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Tuberculosis Drug Discovery|
Tuberculosis (TB) is a deadly disease that kills nearly 2 million people every year. Another 2 billion people, mostly living in the poorest areas, are estimated to be infected with the TB bacterium, Mycobacterium tuberculosis. The drugs used currently to treat TB were developed over 40 years ago, and normally take 6 months to cure someone of disease. The lengthy treatment of TB makes curing those in the poorest communities a daunting challenge. To compound the problem, we are faced with an increasing threat from bacteria that are resistant to many of the drugs used to treat disease; in such cases antibiotic treatment can take 12-24 months.
Our Focus & Solutions
The Tuberculosis Drug Discovery Group is focused on discovering and developing novel drugs that are effective at curing drug sensitive and drug resistant TB with the added goal of shortening the time it takes to cure disease. To maximize our chances for success, we have formed a multi-disciplinary team that combines the efforts of microbiologists, biochemists and chemists to:
- Study the biology of TB bacteria in great detail to identify new metabolic pathways that may be vulnerable to drugs
- Develop and apply innovative methods to discover new drug targets in the TB bacteria
- Test thousands of potential drugs in our screening facility to find new compounds or new compound classes that kill TB bacteria
- Develop biochemical screens to test compounds for their ability to prevent TB protein's functioning normally
- Develop novel screens using conditions that mimic those the TB bacteria encounters in the human body
- Utilize medical chemistry to optimize the structures of compounds so that they kill TB bacteria in a more potent fashion and are non-toxic
The Tuberculosis Drug Discovery Group is dedicated to discovering new drugs to combat TB. We have established a partnership with Eli Lilly, the National Institute for Allergy and Infectious Disease, and Academia Sinica as part of the Lilly TB Drug Discovery Initiative. We collaborate with numerous research institutions, universities and private entities worldwide in our efforts to find new TB drugs. We welcome opportunities to expand our research by developing new collaborations and partnerships.
A. Kumar, A. Casey, J. Odingo, E.A. Kesicki, G. Abrahams, M. Vieth, T. Masquelin, V. Mizrahi, P.A. Hipskind, D.R. Sherman and T. Parish. A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis. PLOS One.
G. Moraski, L. Markley, J. Cramer, P. Hipskind, H. Boshoff, M. Bailey, T. Alling, J. Ollinger, T. Parish and M. Miller. 2013. Advancement of Imidazo[1,2-a]pyridines with Improved Pharmacokinetics and Nanomolar Activity Against Mycobacterium tuberculosis. ACS Medicinal Chemistry Letters. 4(7):675-679.
D. Kumar, K. K. Raj, M. Bailey, T. Alling, T. Parish, D.S. Rawat. 2013. Antimycobacterial activity evaluation, time-kill kinetic and 3D-QSAR study of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives. Bioorganic & Medicinal Chemistry Letters. 23:1365-1369.
D.M. Roberts, Y. Personne, J. Ollinger, and T. Parish. 2013. Proteases in Mycobacterium pathogenesis: potential as drug targets. Future Microbiology. 8:621-631
J. Ollinger, M.A. Bailey, G.C. Moraski, A. Casey, S. Florio, T. Alling, M.J. Miller and T. Parish. 2013. A dual read-out assay to evaluate the potency of compounds active against Mycobacterium tuberculosis. PLoS ONE. 8(4): e60531
J. Ollinger, T O’Malley, J. Ahn, J. Odingo and T. Parish. 2012. Inhibition of the sole type I signal peptidase of Mycobacterium tuberculosis is bactericidal under replicating and non-replicating conditions. J Bacteriol. 194: 2614-2619
J. Ollinger, T. O’Malley, E.A. Kesicki, J. Odingo and T. Parish. 2012. Genetic and chemical validation of the essential ClpP protease in Mycobacterium tuberculosis as a novel drug target. J. Bacteriol. 194: 663-668
T.R. Ioerger, Y. Feng, K. Ganesula, X. Chen, K.M. Dobos, S. Fortune, W.R. Jacobs, V. Mizrahi, T. Parish, E. Rubin C. Sassetti and J.C. Sacchettini. 2010. Variation among genome sequences of H37Rv strains of M. tuberculosis from multiple laboratories. J. Bacteriol. 192:3645-3653
R. Goude and T. Parish. 2009. The EmbC arabinosyltransferase is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob. Ag. Chemother. 53: 4138-4146
Tanya Parish — Program Director