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NIH Record - 75th Anniversary - National Institutes of Health

New Medication Shows Promise Against Liver Fibrosis

A new drug developed by scientists at NIAAA limits the progression of liver fibrosis in mice, a hopeful advance against a condition for which there is no current treatment and that often leads to serious liver disease in people with chronic alcoholism and other common diseases.

“This study represents an important step towards an effective treatment for liver fibrosis,” said NIAAA director Dr. George Koob. A report of the study is now online in JCI Insight.

Liver fibrosis is a gradual scarring of the liver that puts people at risk for progressive liver disease and liver failure. It may develop as a late consequence of chronic alcoholism, viral hepatitis, obesity or diabetes and can progress to cirrhosis and liver cancer, yet currently there is no therapy approved by the Food and Drug Administration.

The new compound is a chemically modified version of ibipinapant, a brain-penetrating cannabinoid type 1 (CB-1) receptor antagonist used in scientific research. Senior author and NIAAA scientific director Dr. George Kunos’ team modified its structure to reduce its ability to penetrate the brain and to include a molecular group that directly inhibits iNOS, the enzyme responsible for generating nitrogen compounds that promote inflammation.

“Fibrosis is a multifactorial, complex disorder that can benefit from simultaneous targeting of more than one cellular process,” Kunos explained.

Kunos and his NIAAA team developed a new medication that concurrently inhibits both CB-1 receptors and iNOS. The new compound was designed to have only very limited ability to enter the brain in order to avoid the psychiatric side effects that limit the usefulness of currently available, brain-penetrant CB-1 receptor-blocking compounds.

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