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“Over the past decade, we have seen an increasing interest in using carboranes in drug design,” says Mark W. Lee Jr., assistant professor of chemistry at the University of Missouri. “Carboranes are clusters of three elements—boron, carbon and hydrogen. Carboranes don’t fight cancer directly, but they aid in the ability of a drug to bind more tightly to its target, creating a more potent mechanism for destroying the cancer cells.”

For the study published in the Journal of Medicinal Chemistry, Lee and colleagues used carboranes to build new drugs designed to shut off a cancer cell’s energy production, which is vital for its survival.

All cells produce energy through complex, multi-step processes. The key to an effective drug is targeting the process that cancer cells depend on more than healthy cells. By increasing the binding strength of a drug, a smaller dose is required, minimizing side effects and increasing the effectiveness of the therapy. With carboranes, Lee found that the drug is able to bind 10 times more powerfully.

“The reason why these drugs bind stronger to their target is because carboranes exploit a unique and very strong form of hydrogen bonding, the strongest form of interactions for drugs,” Lee says.

The discovery also will lead to further uses for the drug.

“Too often, after radiation or chemotherapy, cancer cells repair themselves and reinvade the body,” Lee says. “This drug not only selectively shuts off the energy production for the cancer cells, but it also inhibits the processes that allow those cancer cells to repair themselves.

“When we tested our carborane-based drugs, we found that they were unimaginably potent. So far, we have tested this on breast, lung, and colon cancer, all with exceptional results.”

According to Lee, this is the first study to show systematically how carboranes can improve the activity of a drug. He believes the discovery will open additional possibilities of improving drugs that are used to treat other diseases, not just cancer.

“The end result is that these new drugs could be many thousands of times more potent than the drugs that are used in the clinics today.”

While it will be several years before the new drug will be available on the market, Lee says that clinical trials could begin within the next two years. Additionally, further testing on other types of cancer is under way.

Source: University of Missouri