Discovery of -Lactam Hydroxamic Acids as Selective Inhibitors of Tumor Necrosis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting more than 2 million people in the United States alone. It is traditionally treated with nonsteroidal antiinflammatory drugs (NSAID) or disease-modifying antirheumatoid drugs (DMARD). Owing to limited effectiveness and/or side effects of the two drug classes, there has been a continued search for improved therapeutics. o­ne attractive target is the cytokine tumor necrosis factor (TNF), which has been shown to be overproduced in the joint of RA patients. The clinical success of anti-TNF biologics has validated TNF as a drug discovery target. While they are effective, these proteins are expensive to make and must be administered parenterally.

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