LJ570 is the first PPARα/γ Dual Agonist Able To Bind to Canonical and Alternative Sites of PPARγ and To Inhibit Its Cdk5-Mediated Phosphorylation. LJ570 is a potent partial agonist of both PPARα and γ subtypes. LJ570 inhibited the Cdk5-mediated phosphorylation of PPARγ at serine 273 that is currently considered the mechanism by which some PPARγ partial agonists exert antidiabetic effects similar to thiazolidinediones, without showing their typical side effects. LJ570 may be useful for treatment of dyslipidemic type 2 diabetes.

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Identification of the First PPARα/γ Dual Agonist Able To Bind to Canonical and Alternative Sites of PPARγ and To Inhibit Its Cdk5-Mediated Phosphorylation Antonio Laghezza, Luca Piemontese, Carmen Cerchia, Roberta Montanari, Davide Capelli, Marco Giudici, Maurizio Crestani, Paolo Tortorella, Franck Peiretti, Giorgio Pochetti, Antonio Lavecchia, and Fulvio Loiodice Publication Date (Web): September 10, 2018 (Article) DOI: 10.1021/acs.jmedchem.8b00835