Successful Treatment Of Animal Models Of Acute Graft-Versus-Host Disease With Small-Molecule Tnf Inhibitor

Tumor necrosis factors(TNF, including TNFα and TNFβ) have now been shown to be two of the major mediators of inflammation and can induce other inflammatory cytokines and proteases that orchestrate inflammatory responses. Recently, many reports have indicated that overexpression of TNF involved in the development of acute graft-versus-host disease(aGVHD), and TNF inhibitors have tremendous potential for the treatment of this disease. To date, 5 of the current biomacromolecular TNF inhibitors, including infliximab (IFX), etanercept(ETN), adalimumab, golimumab, and certolizumab pegol, are available for the part of the routine treatment of patients with rheumatoid arthritis, Crohn’s disease, aGVHD and other inflammatory diseases. However, over the past years, several severe limitations of those biomacromolecular TNF inhibitors have also emerged, such as poor stability, exclusion from blood/brain barrier and inducing the development of antidrug antibodies (ADA). For this reason, small-molecule chemical compounds have been designed and developed as appropriate alternatives for overcoming those limitations associated with biomacromolecular inhibitors.