March 7, 2023
John Walker to present Biochemistry and Molecular Biophysics Seminar on March 8
John Walker, professor of pharmacology and physiology at Saint Louis University, School of Medicine, will present "Development and pharmacological profiling a novel series of pan-ERR agonists as potential therapeutics for metabolic diseases" at 4 p.m. Wednesday, March 8, in 120 Ackert Hall.
Presentation abstract: Estrogen-related receptors, or ERRs, are orphan members of the nuclear receptor, or NR, superfamily of proteins. NRs are ligand-mediated transcriptional factors that regulate activation of a variety of target genes. ERRα and ERRγ are highly expressed in tissues with high energy demand such as brain, heart, liver and skeletal muscle while ERRβ has a more restricted expression pattern. Both ERRα and ERRγ have been shown to regulate transcriptional control of metabolic genes involving mitochondrial activity and biogenesis as well as generation and utilization of cellular energy and homeostasis, especially in liver and skeletal muscle. As a result, they have received increasing interest as a therapeutic target for a range of metabolic diseases such as type-2 diabetes, metabolic syndrome and insulin resistance among others. Despite having no known ligands, they do bind several synthetic ER ligands. This led us to apply a structure-based drug design approach to develop both novel pan-agonist and inverse agonist modulators of ERRs. Medicinal chemistry efforts with pharmacological profiling will be presented highlighting these new ERR compounds.