Computational chemistry in the search for improved therapeutics for inflammatory and autoimmune diseases

Abstract

Rheumatoid arthritis (RA), Crohn's disease and multiple sclerosis are common diseases, which are directly related to interactions developed between a protein called the Tumour Necrosis Factor (TNF) and its receptors. Current drugs that effectively disrupt TNF-receptor associations also cause serious side effects. In this feature, we present a computational scheme that resulted in the discovery of two non-toxic compounds, which directly inhibit TNF function. Moreover, the polypharmacology of these compounds was demonstrated as they were also found to inhibit the function of RANKL, a member of the TNF protein family. Optimization of the compounds may lead to the development of new medications for inflammatory and autoimmune treatments.