Their finding, reported in the March 22, 2005, issue of Proceedings of the National Academy of Sciences, is the first step toward developing a new class of anti-cancer drugs that block the Icmt protein from activating uncontrolled cell growth, a hallmark of cancer, according to Patrick Casey, Ph.D. Casey is the study's senior investigator and Duke pharmacologist and cancer biologist.
Moreover, said Casey, their discovery is the first to emerge from the Duke Small Molecule Screening Facility, which houses a library of more than 13,000 compounds available for screening promising drugs with potential to fight cancer and other diseases. Using automated robotics, the facility provides the kind of drug discovery capability usually available only to pharmaceutical company scientists.
Duke's new facility is a finalist for one of six $9 million National Institutes of Health (NIH) grants that will create a national network of publicly accessible small molecule facilities and make them available to researchers nationwide.
Duke University has filed a patent application for cysmethynil, Casey said, and intends to shepherd it through the first steps of drug development by testing the compound in animal models of cancer.
The research was supported by grant from the NIH and a Howard Hughes Medical Institute predoctoral fellowship to Casey graduate student Ann M. Winter-Vann, the first author of the study.
"This is the first selective small molecule inhibitor of Icmt, a protein that has been shown to be an important player in keeping a cancer-causing gene called 'Ras' turned on inside cells," said Casey.
Ras is a normal genetic component