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. 2022 Jan 31;2(3):282–296. doi: 10.1021/acsbiomedchemau.1c00050

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© 2022 The Authors. Published by American Chemical Society

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Compound 7 potently and selectively agonizes the transcriptional function of ERRα. (A) Design strategy and chemical synthesis of compound 7 (JND003); (B) ERRα expression stimulated by 7 in AAB-Luc cells. (C) Compound 7 enhances interaction of ERRα with the PGC1α peptide determined by an AlphaScreen assay. (D,E) Compound 7 improves thermal stability of ERRα in HepG2 cells determined using a CETSA. (F) Compound 7 exhibits selective transcriptional improvement of ERRα over ERRβ and ERRγ. (G) Compound 7 elevates mRNA levels of ERRα-targeted genes, that is, Mcad, Atp5β, and Pdk4. *p < 0.05 vs DMSO.