Estrogen Related Receptors (ERRs) are members of the nuclear hormone receptors (NRs) superfamily. The ERRs subfamily comprise three members, ERRα, ERRβ and ERRγ; and are closely related to the estrogen receptors (ERα and ERβ). ERRα and ERRγ regulate key physiological processes involved in cardiomyocyte metabolism and mitochondrial function. We have developed ERRα/γ dual agonists using structure-based design. The best dual agonists up-regulated the expression of target genes PGC-1α and PGC-1β, which are necessary to achieve maximal mitochondrial biogenesis. Also, they up-regulated CPT1α, which catalyzes the first step of long-chain fatty acid import into mitochondria. Moreover, these compounds increased the mRNA levels of PDK4, which play an important role in energy homeostasis and catalyze the conversion of pyruvate to CoA. Currently, we are using these compounds as chemical tools to validate ERRs as a putative target for the treatment of heart failure.<br/>

Structure-based design estrogen related receptors α/γ dual agonists for the treatment of heart failure

2019 Fall National Meeting

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