Introduction
All projects in the institute pertain to one of the following 3 categories:
- Identification, characterization and optimization of new TB drug leads
- Development of new tools to facilitate TB drug discovery
- Identification of the molecular targets of and/or mechanisms of resistance to anti-TB agents
TB drug discovery efforts include high throughput screening of synthetic compounds and natural products against both replicating and non-replicating Mycobacterium tuberculosis conducted within a biosafety level 3 laboratory. Leads are also derived from the bioassay-guided isolation of natural products from microorganisms, marine invertebrates and higher plants.
Complementing whole cell-based screening efforts are target-based projects, in some cases with in silico modeling components. All have a functional screening component and all target-based projects are performed as collaborations with faculty in the College of Pharmacy specializing in computational chemistry, medicinal chemistry and structural biology or with collaborators outside of UIC. Other projects are examining genes which may be essential for virulence or latency to assess their potential as drug targets.
Lead identification/optimization projects consist of bioassay support for chemists outside of UIC. The remaining projects involve medicinal chemistry that is performed within the Institute. Besides assessment of anti-TB activity in vitro and in vivo, lead optimization efforts include drug metabolism/PK studies and pharmacophore ID/QSAR analyses.
Finally the ITR is a leader worldwide in the development of new HTS-compatible assays to detect new compounds active against both replicating and non-replicating M. tuberculosis.
