A Novel Small Molecule Drug Derived from Methimazole (Phenylmethimazole) that Targets Aberrant Toll-like Receptor Expression and Signaling for the Potential Prevention or Treatment of Diabetes Mellitus and Non-alcoholic Fatty Liver Disease

Abstract

Toll-like receptors (TLRs) are pattern-recognition receptors located on the surface or within (endosome) immune cells (dendritic), whose function is to recognize pathogens from the environment and mediate both the innate and acquired immune responses. Environmental activation of TLRs in nonimmune cells is now recognized as a significant pathway that mediates the loss of self-tolerance in autoimmune diseases, as well as inflammationinduced cell damage in many chronic diseases. We have developed a small molecule drug derived from methimazole, phenylmethimazole (C10), which interferes with the environmental induction of TLR signaling in nonimmune cells and is an active inhibitor of pathologic inflammation in many animal disease models. This article has been written to introduce clinicians to TLR function and the potential therapeutic role that their inhibition could play in many inflammatory/autoimmune diseases, including diabetes and nonalcoholic fatty liver disease (NAFLD).