DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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The compound TIR-199 that holds much promise in the laboratory in fighting renal (kidney) cancer. feb19,2013
RIVERSIDE, Calif. — Chemists at the University of California, Riverside 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.
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.
“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.
Michael Pirrung is a distinguished professor of chemistry at UC Riverside. Photo credit: I. Pittalwala, UC Riverside.
Structure of Syringolin A.
The ring structure of syringolin A is formed by the two nonproteinogenic amino acids 5-methyl-4-amino-2-hexenoic acid and 3,4-dehydrolysine. The α-amino group of the latter is joined by a peptide bond to a valine residue, which is linked to another valine residue via a urea moiety.
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