Cincinnati Children's debuts new anti-inflammatory drug class

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After mixed attempts by others in the past, scientists at Cincinnati Children's Hospital Medical Center say they've developed a new class of compounds designed to prevent inflammation leading to cancer and other diseases, without becoming toxic. They also have names for them: Phox-I1 and Phox-I2.

Computer-assisted drug design was key here, and the researchers confirmed the potential of their new compounds through tests on inflammatory cells from humans and mice. Lead researcher Yi Zheng said in a statement that this class of drugs has the potential to address "an unmet medical need that will have far-reaching implications for treatment of disease."

For details, read the Feb. 24 edition of Chemistry & Biology.

Scientists have been searching for compounds that would block NOX2 enzyme production of reactive oxygen species, or ROS molecules. ROS production is a normal immune system response, the researchers note. But chronic infections or acute ischemia or other outside stresses can trigger too much NOX2/ROS production. This, in turn, can produce tissue-damaging inflammation and lead to everything from chronic obstructive pulmonary disease and hypertension to cancer.

The researchers argue that earlier efforts to develop NOX2 inhibitors successfully blocked excessive ROS production but also affected other cellular functions, causing toxicity. They claim that their compounds are more precise, noting that tests with healthy human blood cells, leukemia cells and mouse blood cells helped shut down the ROS production minus toxicity.

We're hopeful that subsequent animal and human tests are as promising. But that answer isn't possible for a while. Even Zheng points out that much more research is needed before Phox-I compounds can even be tested in people. Until then, Cincinnati Children's is trying to plow ahead. The hospital says it's filed a patent application for Phox-I compounds and is also "exploring opportunities" to accelerate further testing.

- here's the release
- read the journal abstract

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