Pitt develops molecule that fights cancer cell growth

A team of researchers from the University of Pittsburgh has just developed a synthetic anti-cancer molecule called meayamycin, which will supposedly be more powerful than the leading cancer drugs.

The team is led by Kazunori Koide, an associate professor in Pitt’s Department of Chemistry whose research focuses on organic synthesis of natural products, new synthetic methods, diversity-oriented synthesis, and organic fluorescent sensors.

According to Koide’s website, his research team is “currently studying FR901464, a natural product that regulates cancer-related genes by novel mechanisms.”

Similar to other cancer drugs, meayamycin stops the growth and proliferation of cancer cells. However, once the project is complete, researchers suspect that this treatment will be 10 to 100 times stronger than similar drugs.

The need for FR901464 stems from a lack of variety in chemotherapeutic agents, or chemicals that are used by doctors to treat cancer.

In the lab’s research report, Koide stated, “Currently available chemotherapeutic methods are limited to targeting DNA, nuclear hormone receptors, a tyrosine kinase, a proteasome, and the microtubule.”

In other words, there is currently a shortcoming of pharmacological treament in targeting tumorigenesis, or the formation of tumors, Koide said.

After researching the treament mechanisms of FR901464, researchers have developed an analog of the molecule, called meayamycin. Because it is exceptionally active, meayamycin can hinder cell proliferation at a concentration of 10 particulate matter (pM).

According to Koide, this concentration is analogous to a small packet of sugar from a coffeeshop placed in 400 Olympic-Size swimming pools.

In order to develop a more stable analog, the research team studied the decomposition pathways of FR901464. To ensure that this decomposition pathway did not occur, “a right fragment [of the material] was rationally designed and synthesized.”

Researchers then used this stable analogue to form meayamycin in 13 steps.

Unlike similar cancer treaments, meayamycin does not bind to DNA, Koide said. Accoding to Koide, FR901464 works by lowering the mRNA levels of various genes, including oncogenes, which are responsible for forming malignant tumors.

At the moment, researchers are trying to figure out how to prepare a larger form of this analogue.

The paper stated, “The potency and stability of this analogue should facilitate our efforts to isolate cellular targets of FR901464.”

One may wonder what this means for the future of cancer treatment.

“Meayamycin offers alternative therapeutic approaches that are currently not available. Its unique modes of action indicate that some of currently untreatable cancers might be curable,” Koide said.

In addition, the strength of this molecule means that cancer patients can use smaller doses of the drug in order to obtain the same effects as similar drugs such as Taxol. Extra strength may decrease the cost of receiving treatment, as well as any side effects.

The Koide lab has been working on the development of this molecule for six years, with endowments and sponsorship from the University of Pittsburgh, UPMC, the American Chemical Society, the American Cancer Society, and the National Institutes of Health.

A University of Pittsburgh press release stated, “In tests, meayamycin successfully worked against breast and cervical cancer cells as well as those from multidrug-resistant cancers.”

Meayamycin may treat other cancers as well. The press release stated, “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.”

Researchers have also found that the molecule may work for patients whose cancers do not respond to pre-existing treatments.

Now that the molecule has been created, further development of the molecule is necessary to appreciate its properties, Koide said.

In particular, he said his lab’s next steps will be “to determine tumor specificity in vitro and in vivo, and to study the pharmacokinetics of meayamycin. We will also determine the mode of action.”

The lab’s findings will be published in the Journal of the American Chemical Society next month.