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The discovery of biased modulators of TLR4 would provide insight for the future development of biased modulators for other non-GPCR receptors.Diabetes mellitus (DM) is associated with a specific cardiac phenotype characterized by structural and functional alterations. This so-called diabetic cardiomyopathy (DM CM) is clinically relevant as patients with DM show high incidence of heart failure. Mechanistically, several parameters interact on the cardiomyocyte level leading to increased inflammation, apoptosis, reactive oxygen species an