At present lot of work is being carried out on small molecule inhibitors of tnf alpha converting enzyme (TACE). As we all know, TACE is the enzyme which convert pro-TNF to soluble TNF. There are conflicting reports in the literature suggesting role of membrane bound TNF in tha pathogenesis of arthritis. Is there any clinical report suggesting role of membrane bound tnf in arthritis ?? Also I would like to know the clinical efficacy of TACE inhibitors as a target.
Your question is a very good one but beyond the scope of this forum. I think it would be hard to separate isolate the effects of membrane bound TNF from soluble TNF in RA since the membrane form of TNF is readily cleaved from the surface. I am sure that there are more than one TACE inhibitors in clinical trials. The one agent that I am aware of was disappointing in clinical trials. However, I think TACE remains a viable drug target.