TIR-199: Potential New Heavy Weapon Against Kidney Cancer

| Mar 8, 2013

Researchers in California may have taken a big step in the fight to end renal cancer.

Chemists at the University of California, Riverside, have developed a compound they've named TIR-199 that exclusively targets and inhibits the activity of kidney cancer cells.

The development was announced in February at a lecture given by chemistry professor Michael Pirrung at the 5th International Conference on Drug Discovery and Therapy in Dubai.

TIR-199 is similar to the drug bortezomib, the first FDA-approved drug which inhibits the proteasome, or cellular complexes that break down proteins, in multiple myeloma, a cancer that originates in bone marrow.

But while bortezomib has unwelcome side effects because it impacts cells other than multiple myeloma cells, TIR-199 only impacts kidney cancer cells.

"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 in a press release. "It's what makes TIR-199 attractive."

Research began four years ago at the University of California, Riverside,  and included testing at the University of Hawaii, Hilo, and the National Cancer Institute at the National Institutes of Health, where the compound was tested for its effectiveness in battling 60 different types of cancer, including leukemia, lung, colon, brain, breast, ovarian, and renal cancers.

"We were very excited when the NCI informed us that TIR-199 has excellent potential to be moved to drug development because of its selective activity against renal cancer," Pirrung said. "This is good news also because the NCI scientists told us there really are no good drugs out there to fight renal cancer."

 After initial testing on lab-grown cells, TIR-199 will be tested on mice.

"We still have to fine-tune TIR-199 in the lab because some aspects-certain structural elements within it-make it easily metabolized," Pirrung said. "But now that we have a good handle on how structural changes in the compound affect anticancer activity and how the parent drug binds to the proteasome, we are pretty confident of making a better version-the second generation-of TIR-199."

The project was funded by a grant from the University of California Institute for Mexico and the United States (UC MEXUS), to Tannya Ibarra-Rivera, a former postdoctoral researcher in Pirrung's lab who helped discover TIR-199 and after whose initials the compound is named; and to Pirrung from the UC Cancer Research Coordinating Committee.

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