November 23, 2017 |
Some Anti-Inflammatory Drugs Affect More Than Their Targets
August 25, 2014  | 

Baltimore, MD - Researchers have discovered that three commonly used nonsteroidal anti-inflammatory drugs, or NSAIDs, alter the activity of enzymes within cell membranes. Their finding suggests that, if taken at higher-than-approved doses and/or for long periods of time, these prescription-level NSAIDs and other drugs that affect the membrane may produce wide-ranging and unwanted side effects.

More positively, the researchers say, their work provides the basis for a test that drug developers can use to predict and perhaps avoid these side effects in new medicines they make. A summary of the results was published online in the journal Cell Reports on Aug. 21.

“When drug designers think about possible sources of side effects, they tend to think about which proteins are similar to the protein they are targeting, and they make sure that the former are not affected by the drug,” says Sinisa Urban, Ph.D., an associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator. “But our group has found that drugs that affect the cell membrane can alter the activity of proteins that are totally unrelated to the target.”

Working with Syed Moin, then a postdoctoral fellow in his laboratory, Urban’s project began as an investigation into the role of the cell membrane in the activity of a group of “cellular scissors” embedded within it, known as rhomboid proteases. When rhomboid proteases cut proteins, the split proteins are released from the membrane. From there, half a protein might go on to signal to another cell or both halves might end up being degraded to prevent further functioning. It all depends on the jobs of the specific proteins that are cut, which are known to play roles in everything from malaria to Parkinson’s disease. Continue>

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