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New class of compounds stops disease-fueling inflammation in lab tests
Date:2/23/2012

CINCINNATI Scientists have developed a unique compound that in laboratory tests blocks inflammation-causing molecules in blood cells known to fuel ailments like cancer and cardiovascular disease without causing harmful toxicity.

Past attempts to identify new compounds that tamp down so-called reactive oxygen species (ROS) molecules in cells have been complicated by toxicity issues and a lack of specificity in targeting molecular processes. Researchers from Cincinnati Children's Hospital Medical Center report in the Feb. 24 Chemistry and Biology (a Cell Press publication) they have overcome this problem.

They did so by using computer-assisted drug design verified by laboratory tests on human and mouse inflammatory cells to precisely target a single component of an enzyme network called NOX2. The enzyme network drives ROS production in immune system white blood cells known as neutrophils. The eventual goal, researchers say, is establishing new small-molecule inhibiting drugs that can stop excessive inflammation and treat a number of inflammation-mediated diseases that need improved therapies.

"Drugs that potently and specifically target ROS production by NOX2 enzyme are an unmet clinical need that will have far-reaching implications for treatment of disease," said Yi Zheng, PhD, a lead investigator on the study and director of Experimental Hematology/Cancer Biology at Cincinnati Children's. "The lead candidate we developed, Phox-I, shows promising inflammation inhibiting activity in cells and mouse models."

The production of ROS in cells is a normal part of the body's immune system, as oxidative enzymes are generated by white blood cells to attack illness-causing microorganisms. In a number of pathologic conditions, however, various environmental stressors (like acute ischemia, chronic infections, etc.) can help trigger an overabundance of biochemical signaling. The signaling occurs through a regulatory pathway invo
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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