New Drug Discovery Initiative to Support Identification of New Drugs for Cancer and Infectious Disease

A drug discovery effort has taken shape at IITRI that portends the development of new alliances with pharmaceutical and biotechnology companies. Established in the first quarter of 2007, IITRI's Drug Discovery Division (DDD) was created to synthesize and develop New Chemical Entities (NCEs) with pharmacologic activity.

The DDD team, managed by Rajendra Mehta, Ph.D., Assistant Vice-President, will synthesize novel therapeutically active compounds directed at (a) cancer prevention and therapy and (b) infectious diseases of interest to the biodefense community. Dr. Mehta's past collaborative work with synthetic organic chemist Dr. Robert Moriarty, Professor Emeritus in the Department of Chemistry at the University of Illinois at Chicago (UIC), continues at IITRI. Dr. Moriarty has joined the IITRI staff as Senior Science Advisor, and will provide oversight of chemical synthesis work being performed by IITRI scientists Rajesh Naithani, Ph.D., Research Chemist, and Loredana Huma, M.S., Associate Chemist. Strategies include both the development of new compound classes and chemical modification of natural products that are known to have desirable biological activity.

	Loredana Huma, M.S., Associate Chemist, and Rajesh Naithani, Ph.D., Research Chemist, working in the DDD laboratory

Using multi-step organic synthesis, analogs of biologically active natural products are being prepared by varying functional groups around the main molecular core to improve agent activity. Synthetic approaches have begun with small molecules from several classes, including flavones, indoles, thioles, and vitamins; a number of members of these classes of natural products have been evaluated for anti-cancer activity by scientists working in IITRI's Carcinogenesis and Chemoprevention Division, and/or have undergone GLP-compliant pre-clinical toxicology testing by scientists working in IITRI's Toxicology Division.

The DDD team currently has three lead molecules from which it is generating libraries of analogs for pre-clinical efficacy testing at IITRI. Scientists in the DDD currently conduct small-scale synthesis, carrying compounds through synthesis, purification and characterization in an organic synthesis laboratory located in the IIT Technology Incubator, adjacent to IITRI. Anti-viral testing is being performed under BSL-2 and BSL-3 conditions by scientists working in IITRI's Microbiology and Molecular Biology Division; anti-cancer activity is being evaluated by members of IITRI's Carcinogenesis and Chemoprevention Division. Once chemical libraries of appropriate size have been evaluated, the most effective analogs will be evaluated in pre-clinical toxicology studies to be performed by IITRI's Toxicology Division. In order to support the synthesis demands of more broadly-based pre-clinical evaluations, plans are underway to equip the current DDD laboratory with instrumentation for scale-up synthesis of intermediates and final compounds. As research proceeds, additional staff will be hired, and new therapeutic areas will be explored.

Once effective anti-cancer or anti-infective agents have been identified and evaluated in pre-clinical models, IITRI plans to seek licensing arrangements/alliances with pharmaceutical or biotechnology companies to bring these agents into the clinic. These new alliances are expected to present more opportunities to offer IITRI's expert services in toxicology and carcinogenesis, microbiology and molecular biology and inhalation toxicology.