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In Battling Kidney Cancer, New Compound Holds High Promise

by Bidita Debnath on February 21, 2013 at 11:06 PM
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In Battling Kidney Cancer, New Compound Holds High Promise

At the University of California, Riverside, chemists have developed a compound that holds much promise in the laboratory in fighting renal (kidney) cancer.

Named TIR-199, the compound targets the "proteasome" a cellular complex in kidney cancer cells, similar to the way the drug bortezomib, approved by the Food and Drug Administration, targets and inhibits the proteasome in multiple myeloma cells, a cancer coming from bone marrow.

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Michael Pirrung, a distinguished professor of chemistry at UC Riverside, announced the development of TIR-199 in a lecture he gave on Feb. 19 at the 5th International Conference on Drug Discovery and Therapy, held in Dubai, UAE.

Operating like the garbage dump of a cell, the proteasome breaks down proteins. Drugs that block the action of proteasomes are called proteasome inhibitors, and have been shown to have activity against a variety of cancer cell lines, albeit with mixed results. For example, bortezomib, though effective against multiple myeloma, has many side effects because cells other than bone marrow cells are affected.
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"The novel feature of our new proteasome inhibitor, TIR-199, is that it is nearly as potent as bortezomib, but is selective in inhibiting the growth of only renal cancer cell lines," Pirrung said. "It's what makes TIR-199 attractive."

The TIR-199 research project at UC Riverside began about four years ago after a multidisciplinary, international team reported on a class of compounds that act on the proteasome. These compounds are the "syringolin" natural products — such as a compound produced naturally by the wheat-infecting bacterium Pseudomonas syringae. TIR-199 is a synthetic relative of syringolin.

"At UCR we began to work on, and completed the synthesis of, two compounds from this class of compounds," Pirrung said. "Of the two, TIR-199 showed most promise."

Source: Eurekalert
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