Lippard is senior author of a
paper describing the new drug candidate, known as phenanthriplatin, in the Proceedings of the National Academy of Sciences (PNAS). Lead author is postdoc Ga Young Park; other authors are graduate student Justin Wilson and postdoc Ying Song.
One reason for the efficacy of phenanthriplatin is that it can get into cancer cells more easily than cisplatin, Lippard says. Previous studies have shown that platinum compounds containing carbon can pass through specific channels, found in abundance on cancer cells, that allow positively charged organic compounds to enter. Another reason is the ability of phenanthriplatin to inhibit transcription, the process by which cells convert DNA to RNA in the first step of gene expression.
Another advantage of phenanthriplatin is that it seems to be able to evade some of cancer cells’ defenses against cisplatin. Sulfur-containing compounds found in cells, such as glutathione, can attack platinum and destroy it before it can reach and bind to DNA. However, phenanthriplatin contains a bulky three-ring attachment that appears to prevent sulfur from inactivating the platinum compounds as effectively.
Luigi Marzilli, a professor of chemistry at Louisiana State University, says the new compound appears to be very promising. “It expands the utility of platinum drugs and avoids some of the problems that existing drugs have,” says Marzilli, who was not part of the research team.
The researchers are now conducting animal tests to determine how the drug is distributed throughout the body, and how well it kills tumors. Depending on the results, they may be able to modify the compound to improve those properties, Lippard says.
Source:
http://web.mit.edu/newsoffice/2012/platinum-cancer-drug-candidate-0711.html
