School of Pharmacy

Nouri Neamati, PhD

Research Interest

Dr. Neamati's lab uses computational chemistry to match chemical compounds to biological processes in an effort to design novel drugs and therapeutics. Focusing on small-molecule design, Neamati's research aims to find compounds that will fit into active sites in proteins and enzymes to inhibit their expression.

A small-molecule drug works by binding to a target, usually a specialized protein in a disease cell. Before computational chemistry technology was available, researchers had to design or test a compound derived from a natural product, inject it into mice or patients, and then wait to observe the results. This process was slow, expensive and comparatively ineffective. Now, while in vitro testing saves both time and money, sifting through a library of some 10 million compounds still presents a daunting time-consuming drug development process.

Neamati's computational platform allows him to pursue, through a rational selection process that predicts which compounds are likely to inhibit a particular protein, some fifty-thousand compounds to move to the next step in drug discovery. Then, using mathematical and statistical analysis to cluster these compounds into families, Neamati can test one compound from each family under the assumption that they embody properties of other members of the family. Once a compound of interest is identified, he can examine the whole family of compounds to find the optimal match for a specific target.

Another approach to drug design used in the Neamati lab is based on the structure of the target protein. Neamati uses technology that can design a compound that fits nicely on the active site of a protein, like a lock and key. Using the structural knowledge already available on vast numbers of existing drugs and targets, Neamati proceeds by either building a compound based on a known drug or a compound based on the target.

Neamati's work primarily focuses on cancer and HIV. He currently has compounds at various stages of development - from theoretical to in vitro to in vivo. Some of these compounds have been shown to work in experimental mouse disease models while exhibiting no toxicity. Collaborating with colleagues at the Norris Cancer Center, Neamati aims to take these promising therapeutics into phase 1 clinical trials. His research has also developed compounds for diabetes, and through collaboration, has discovered a drug for muscular dystrophy that is currently in the early stages of development.

Biography

Nouri Neamati is a Professor of Pharmacology and Pharmaceutical Sciences at the University of Southern California, School of Pharmacy. He obtained a Ph.D. in Biomedical Sciences from the University of Texas Graduate School of Biomedical Sciences and M.D. Anderson Cancer Center, Houston, Texas in 1995. From 1995 to 2000 he was a postdoctoral fellow and a research fellow at the National Institutes of Health. In September 2000, he joined the University of Southern California, School of Pharmacy with a joint appointment at the Norris Comprehensive Cancer Center.

Dr. Neamati is the recipient of numerous awards including the NIH Technology Transfer Award in 2000, STOP CANCER Award in 2001, GlaxoSmithKline Drug Discovery Award in 2002, BCRP and LCRP Concept Awards from the Department of Defense (DOD) in 2005 and 2009, LUNGevity Discovery Award, American Lung Association, 2006, The Littlefield-AACR Award in Metastatic Colon Cancer Research, in 2006, and the Idea Awards in Ovarian and Breast Cancer from the DOD in 2006 and 2010. He has published more than 180 peer-reviewed manuscripts, 18 book chapters, and over 20 patents in the area of drug design and discovery. He has recently edited the first comprehensive and authoritative book on “HIV-1 Integrase: Mechanism and Inhibitor Design”. He has served in numerous study sections including the NIH and DOD. He is the Editor-in-Chief of Current Molecular Pharmacology, an Associate Editor of Current Anticancer Drug Targets, and an Editorial Advisory Board member of several journals including Expert Opinion on Drug Discovery, Expert Opinion on Investigational Drugs, Hormones & Cancer, and the Journal of Medicinal Chemistry.

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Research Support

Susan Komen Breast Cancer Foundation, Department of Defense, University-wide AIDS Research Program, American Lung Association, Whittier Foundation.

Selected Projects/Publications

3. Drake, R. R., Neamati, N., Hong, H., Pilon, A. A., Sunthankar, P., Hume, S. D., Milne, G. W., and Pommier, Y. Identification of a nucleotide binding site in HIV-1 integrase. Proc Natl Acad Sci U S A, 95: 4170-4175, 1998.

2. Wang, Y. X., Neamati, N., Jacob, J., Palmer, I., Stahl, S. J., Kaufman, J. D., Huang, P. L., Winslow, H. E., Pommier, Y., Wingfield, P. T., Lee-Huang, S., Bax, A., and Torchia, D. A. Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell, 99: 433-442, 1999.

1. Melek, M., Jones, J. M., O'Dea, M. H., Pais, G., Burke, T. R., Jr., Pommier, Y., Neamati, N., and Gellert, M. Effect of HIV integrase inhibitors on the RAG1/2 recombinase. Proc Natl Acad Sci U S A, 99: 134-137. 2002.