Marine Natural Products as Anti-Cancer Compounds Phil Crews , Department of Chemistry and Biochemistry The Crews laboratory investigates the chemical structure and biological activity of chemical compounds that are derived from marine organisms. Among its many research projects, the laboratory collaborates with scientists at other research institutions and pharmaceutical industries to explore the identification and development of naturally occuring compunds in the fight against cancer. (Keywords: biochemistry, structural biology, natural product chemistry, cancer, drug discovery, chemical synthesis)

The focus of research in the laboratory of Phil Crews is on the chemistry of marine sponges and marine-derived fungi, particularly on compounds with novel structures and relevant biological activity.  Important components of this research include (1) field expeditions to regions of high biodiversity for the collection of sponges and deep-water sediments; (2) bioassay-guided fractionation employing academic, medical, and corporate collaborations primarily for, but not limited to, anticancer drug discovery; (3) state-of-the-art pure compound isolation and structure elucidation techniques; (4) further explorations of chemical ecology, biosynthesis, and the relationship between secondary metabolite chemistry and taxonomy.

Targeted Discovery of Marine-derived Anticancer Leads

Phil Crews is the principle investigator of a multi-institutional National Cooperative Drug Discovery Group, in collaboration with Novartis Institutes for Biomedical Research, researchers from the Center for Marine Biomedicine at the Scripps Institute of Oceanography, the Skaggs School of Pharmacy at UC San Diego, and Harbor Branch Oceanographic Institution in Florida.  The emphasis is on the use of cancer relevant molecular target-based assays for high throughput screening of pre-fractionated marine natural product mixtures and pure compounds.  A current focus is on the discovery of small molecules that disrupt protein-protein interactions that have been shown to have role in the etiology of cancer.  Secondary cell-based assays are then used to screen lead compounds followed by the synthesis of analogues to enhance activity, pharmacokinetics, pharmacodynamics, and in vivo efficacy studies.  A class of compounds known as the bengamides, first isolated from the Fijian marine sponge, Jaspis coriacea, by the Crews’ group in 1986, was further developed by Novartis into a synthetic analog, NVP-LAF389, and proceeded into human clinical trials until 2002.  Psammaplin, another compound discovered by the Crews group, provided important pharmacophore information for the development of two compounds, LAQ 824 and LBH 589, now in Phase I anticancer clinical trials.

This work is sponsored by the National Cancer Institute, grant number U19 CA52955.

Professor Crews has also taken leading role in programs that are designed to increase participation of disadvantaged undergraduate students in research. Click here for information about the SURF and ACCESS programs.