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UC Davis Comprehensive Cancer Center

UC Davis Comprehensive Cancer Center

Combinatorial Chemistry

Director: Kit Lam, M.D., Ph.D. 

Dr. Kit Lam © 2010 UC RegentsDr. Lam is the inventor of the one-bead one-compound (OBOC) combinatorial library method and through the Combinatorial Chemistry Shared Resource, he has been providing OBOC combinatorial libraries and support services to cancer center members. The OBOC method is much more efficient, both in compound synthesis and library screening. Indeed it is the ultra-high throughput method unmatched by any parallel synthesis methods. Quite a few UC Davis investigators have developed successful grant proposals using this method.

Combinatorial library methods not only offer great potential for facilitating the drug discovery process but also provide powerful tools for basic research in various disciplines. These methods enable investigators to generate large number of chemical compounds that can be used as valuable source for the discovery of drug leads, molecular imaging agents, and capturing agents for molecular markers. In the area of basic research, large collections of chemical compounds can be used to probe their effects on specific cellular function. Compounds that elicit or suppress a specific cellular response can then be identified and used as reagents to study cellular pathways involved in these cellular functions. This relatively new field of "chemical genetics" relies heavily on the availability of compound collections, which is difficult to find in academic laboratories.

OBOC combinatorial library © 2010 UC RegentsIn addition to OBOC libraries, the Combinatorial Chemistry Shared Resource has been providing solution phase small molecule libraries to cancer center investigators. The technology involves the development of a novel polymer bead grafted with hydrophilic dendritic polymer of the bead surface such that these beads can be used for in situ solution phase releasable assay. We can place 10,000 compound-beads in a single small Petri dish containing a PDMS microbead high-density micro-well arrays for ultra high-throughput solution phase releasable assays. Over 100,000 chemical compounds can be screened by a technician in a few days. More importantly, this OBOC chemical library method is relatively inexpensive and can be adapted to many existing cell-based or biochemical assays commonly used by many our cancer center members.