ABSTRACT
Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a key role in the pathogenesis and physiology of inflammatory and autoimmune diseases, such as coronary heart disease, cancer, Alzheimer's disease, asthma, rheumatoid arthritis, and most recently COVID-19. IL-6 and its signaling pathway are promising targets in the treatment of inflammatory and autoimmune diseases. Although, anti-IL-6 monoclonal antibodies are currently being used in clinics, huge unmet medical needs remain because of the high cost, administration-related toxicity, lack of opportunity for oral dosing, and potential immunogenicity of monoclonal antibody therapy. Furthermore, nonresponse or loss of response to monoclonal antibody therapy has been reported, which increases the importance of optimizing drug therapy with small molecule drugs. This work aims to provide a perspective for the discovery of novel small molecule IL-6 inhibitors by the analysis of the structure-activity relationships and computational studies for protein-protein inhibitors targeting the IL-6/IL-6 receptor/gp130 complex.
Subject(s)
Autoimmune Diseases , COVID-19 , Humans , Interleukin-6 Inhibitors , Molecular Docking Simulation , Autoimmune Diseases/drug therapy , Antibodies, Monoclonal/pharmacology , Interleukin-6 , Structure-Activity RelationshipABSTRACT
In this paper, we demonstrate an easy way to prepare a stable reduced graphene oxide (RGO) dispersion in aqueous or organic media by simple adjustment of the degree of reduction and pH of RGO dispersion, and a subsequent fabrication of transparent conductive RGO thin films on various substrates using a spray coating technique. RGOs were prepared using a hydrazine reducing agent from graphene oxide (GO), which was oxidized from graphite via a modified Hummers' method. The degree of reduction determined the surface properties, such as atomic composition, surface polarity, and potential of RGO platelets. In addition, pH significantly affected the surface potential of graphene dispersion. The fine adjustment of degree of reduction and pH of RGO dispersion made production of fine RGO dispersions in aqueous and organic media such as ethanol and DMF possible without any aid of dispersing agents. The stable RGO dispersion using volatile ethanol medium provided a unique advantage to be spray-coated into uniform transparent conductive RGO thin films on various substrates including silicon wafer, flexible polycarbonate film regardless of their surface properties, and even on non-planar substrates such as round-shaped glassware at room temperature.