Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis

The success of agents that inhibit tumor necrosis factor (TNF), such as infliximab, adalimumab and etanercept, has led to a desire for orally available small molecules that have a better safety profile and are less costly to produce than current agents. One target for anti-TNF therapy that is currently under investigation is TNF-converting enzyme, which promotes the release of soluble TNF from its membrane-bound precursor. Inhibitors of this enzyme with drug-like properties have been made and tested in the clinic. These inhibitors include TMI-005 and BMS-561392, both of which have entered into phase II clinical trials. This article summarizes preclinical and clinical findings regarding the use of inhibitors of TNF-converting enzyme for the treatment of rheumatoid arthritis.