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New Anti-inflammatory Agents Developed

02/20/08
Scientists at USC and Harvard develop compounds that may fill the void left by the withdrawal of Vioxx and other COX-2 inhibitors.

By Carl Marziali
USC College chemist Nicos Petasis

Photo/Philip Channing
Scientists at USC and Harvard Medical School have developed new anti-inflammatory agents designed to avoid the side effects that caused the withdrawal of Vioxx and related drugs from the market.

The researchers, led by USC College chemist Nicos Petasis and biologist Charles Serhan of Harvard’s Brigham and Women’s Hospital, propose an alternative approach for treating inflammation.

Rather than blocking the action of pro-inflammatory agents such as the COX-2 enzyme the target of drugs known as COX-2 inhibitors, which also block other processes important to human health Petasis and Serhan suggested using synthetic compounds that mimic the action of anti-inflammatory molecules produced by the body.

“If you want to shut down inflammation, you don’t necessarily have to go after the bad molecules,” Petasis said.

Instead, the researchers are making more of the good molecules.

There are no guarantees of success. But one of Petasis’ first compounds led to a drug being tested in a clinical trial for inflammatory bowel disease. Another has shown promise for treatment of periodontal disease.

Both are synthetic versions of natural substances known as lipoxins. When inflammation flares up, the body tries to control it by releasing lipoxins and other anti-inflammatory chemicals.

Lipoxins were discovered more than 20 years ago, but they are too unstable to be used as drugs. Petasis and Serhan have been developing longer-lived relatives, or analogs, of the substances.

Their newest compounds are described in the Feb. 15 issue of the journal Bioorganic & Medicinal Chemistry Letters.

Besides having improved stability and longevity, the compounds also are much easier and cheaper to make.

Petasis, holder of the Harold and Lillian Moulton Chair in Chemistry, hopes this new class of lipoxin analogs will find wide therapeutic use.

“The discovery of stable lipoxin analogs created a new paradigm on how to treat inflammation,” he said.

Other co-authors on the study were USC graduate students Raquel Keledjian, Rong Yang and Kalyan Nagulapalli, and Harvard Medical School researchers Yee-Ping Sun and Eric Tjonahen.

Funding for the research came from the National Institutes of Health.