Koide’s Research Team Creates Anticancer Molecule 10-100 Times More Powerful Than Leading Drugs

Process of developing molecule published in Journal of the American Chemical Society

A Pitt research team has created a synthetic anticancer molecule remarkably more powerful than current cancer drugs that could, once fully developed, offer an alternative to people whose cancer does not respond to available medication.

The Journal of the American Chemical Society published the Pitt researchers’ account of developing the molecule, known as meayamycin, online Feb. 6 with the print version to come out in March. More testing is needed to perfect meayamycin, but the project’s lead investigator is optimistic that the powerful molecule will yield an effective treatment.

Meayamycin stops cancer cells from dividing, much like the leading drug paclitaxel (sold as Taxol), except that in lab tests meayamycin did the job in lower concentrations, said principal investigator Kazunori Koide, an assistant professor of chemistry in Pitt’s School of Arts and Sciences. It was 10-100 times stronger than other commonly used drugs, he said. People might then need less meayamycin to get the same effect of current treatment dosages, thus helping to rein in treatment costs and possibly produce fewer side effects, Koide said. Furthermore, meayamycin does not attach itself to a patient’s DNA or the usual protein targets within cells as current cancer drugs do, Koide added.

Some cancer does not respond to these currently available treatments, he said; meayamycin may present cancer patients with another option.

“Cancer is a lot more complicated than most diseases,” Koide said. “There are hundreds of causes of cancer at the genetic level. It’s impossible for any single cancer drug to work in everyone. But if there are no options available when a treatment fails, a person is left with nothing.”

In tests, meayamycin successfully worked against breast and cervical cancer cells as well as those from multi-drug resistant cancers, Koide said. It is based on a compound developed by a Japanese company to combat colon and lung cancer as well as leukemia. Meayamycin most likely works against those cancers, too, since the differences between it and the Japanese parent molecule are subtle except for meayamycin’s greater potency, Koide said.

For now, Koide revels in the major breakthrough of creating the molecule, a taxing six-year project supported by the National Institutes of Health.

“All new therapies start with new compounds made or isolated by chemists,” Koide said. “The chemistry requires a lot of intellectual curiosity, patience, and dedication, and that has worked out so far. We have the blueprint to go from here to the end.”

Contributors to Koide’s meayamycin research included Pitt 5th-year graduate student Brian J. Albert and junior Nancy L. Czaicki. Czaicki and postdoctorate fellow Miaosheng Li are involved in the large-scale synthesizing of meayamycin. Future collaborators in the research will include Research Assistant Professor Andreas Vogt and Allegheny Foundation Professor John S. Lazo of the pharmacology department in Pitt’s School of Medicine; Billy W. Day, director of the Proteomics Core Lab in Pitt’s schools of the health sciences; and Donald Kufe of the Harvard Medical School.