Case Western, Janssen, Oncodesign scientists ID anti-inflammatory compounds

Investigators have pegged two compounds that appear to reduce inflammation associated with a wide range of diseases such as ulcerative colitis, arthritis and multiple sclerosis.

The compounds, dubbed OD36 and OD38, seem to work by restricting inflammation-triggering signals from an enzyme called RIPK2 that stimulate high-energy molecules into telling the immune system to respond with inflammation.

RIPK2's normal function is to send warning signals to cells alerting them of a bacterial infection. This reaction rallies the body into making white blood cells to use against the infecting pathogen. The white blood cells zero in the invading bacteria and encircle it, causing blood to accumulate in the region of the infection. This blood buildup is what produces red and swollen areas typical of inflammation. When something goes wrong in this process, inflammation can escalate and cause tissue destruction. RIPK2 works alongside NOD1 and NOD2 proteins in modulate responses by the immune system that lead to this inflammation process.

A team from Case Western Reserve University School of Medicine, French outfit Oncodesign, Johnson & Johnson's ($JNJ) Janssen, and Belgian CRO Asclepia Outsourcing Solutions made the discovery, which is detailed in the Journal of Biological Chemistry.

The research team used Oncodesign's library of 4,000 compounds to search for those that targeted kinases, and eventually narrowed the selection down to 13. The investigators then tested the 13 compounds in mouse and human cells and found that OD36 and OD38 were most effective in blocking RIPK2.

The researchers are now on the hunt for a Big Pharma partner that can take the two compounds into Phase I trials.

- read the press release
- get the study abstract

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