PITTSBURGH, October 21, 1998 — A University of Pittsburgh team of investigators has received a five-year, $5 million federal grant to speed drug discovery through revolutionary means—biocombinatorial chemistry. The National Cancer Institute (NCI) grant to Pittsburgh researchers is one of only three issued nationwide. Biocombinatorial chemistry is an emerging field characterized by the rapid, parallel synthesis of large "libraries" of organic compounds used for testing in biological systems.
This initiative, conceived to discover new cancer drugs, is a combined effort by researchers from the School of Medicine’s department of pharmacology, the university’s department of chemistry, the Graduate School of Public Health’s department of environmental and occupational health and a private Pittsburgh-based company, Cellomics, Inc. Through biocombinatorial chemistry, the university investigators will create novel chemical compounds at the department of chemistry’s newly established Combinatorial Chemistry Center and then test them elsewhere in the university in specific assays to learn whether they interrupt cellular activities that can lead to cancer. Pittsburgh researchers also will create a repository for newly manufactured compounds that then can be acquired and tested by outside investigators.
"The University of Pittsburgh is at the academic forefront of a creative revolution in drug manufacturing," said Ronald B. Herberman, M.D., director of the University of Pittsburgh Cancer Institute (UPCI) and associate vice chancellor for research, Health Sciences, University of Pittsburgh. "UPCI is benefiting enormously from a unique, integrated group of exceptional laboratory and clinical investigators. Together, they are developing and executing 21st-century approaches to translating basic research into the clinic.
"Everyday, scientists are discovering the molecular bases of disease and, in the process, revealing many new potential drug targets. Biocombinatorial chemistry is the most comprehensive approach to designing highly specific drugs that work," said John S. Lazo, Ph.D., principal investigator on the grant, Allegheny Foundation professor and chairman of the university’s department of pharmacology and co-director of UPCI’s Molecular Therapeutics/Drug Discovery program. "Biocombinatorial chemistry offers a stark contrast to current methods of drug discovery, which have a long lag time from drug synthesis to application in the clinic with patients. By contrast, biocombinatorial chemistry is expected to offer the public optimally effective, safe medications quickly," he added.
Biocombinatorial chemistry exploits the discovery of genes and their proteins, which serve as molecular targets for drugs because they control biological processes that often lead to disease.
"With this approach, we start with a chemical compound called a platform that locks onto a specific molecular target. We change the platform incrementally to quickly produce hundreds of compounds that we can screen against that given target," said Peter Wipf, Ph.D., co-investigator on the grant and professor in the department of chemistry, where he directs the Combinatorial Chemistry Center. "Through this process, we can readily learn what specific compound structure is best at disrupting a biological pathway."
"Biocombinatorial chemistry has particular importance for diseases like cancer, where you want to provide a highly specific drug that will effectively and selectively kill tumor cells without damaging other healthy cells and potentially creating dangerous side effects," added Dr. Lazo.
This new approach to drug discovery combines university expertise in genomics (the discovery and classification of new genes), chemical design and synthesis, biochemistry, pharmacology, toxicology, computer modeling and robotics with expertise from faculty at Carnegie Mellon University.
The UPCI is one of a select group of NCI-designated comprehensive cancer centers nationwide. As such, it excels in patient care and in cancer detection, diagnosis, prevention and treatment. UPCI is internationally recognized for bringing laboratory research findings to the clinic where patients have the advantage of exceptional treatment opportunities.