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

Nat Clin Pract Rheumatol. 2008 Jun;4(6):300-9. doi: 10.1038/ncprheum0797. Epub 2008 Apr 15.

Abstract

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.

Publication types

  • Review

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM17 Protein
  • Animals
  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / drug therapy*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antirheumatic Agents
  • Enzyme Inhibitors
  • Tumor Necrosis Factor-alpha
  • ADAM Proteins
  • ADAM17 Protein