An article Novel Phenyldiazenyl Fibrate Analogues as PPAR alpha/gamma/delta Pan-Agonists for the Amelioration of Metabolic Syndrome WOS:000464767700027 published article about BINDING; MECHANISMS; INSIGHTS; ACID in [Giampietro, Letizia; Florio, Rosalba; Recinella, Lucia; Ammazzalorso, Alessandra; Bruno, Isabella; De Filippis, Barbara; Fantacuzzi, Marialuigia; Ferrante, Claudio; Maccallini, Cristina; Verginelli, Fabio; Brunetti, Luigi; Cama, Alessandro; Amoroso, Rosa] Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, Italy; [Laghezza, Antonio; Tortorella, Paolo; Loiodice, Fulvio] Univ Bari Aldo Moro, Dept Pharm Drug Sci, Via E Orabona 4, I-70126 Bari, Italy; [Cerchia, Carmen; Capone, Fabio; Lavecchia, Antonio] Univ Napoli Federico II, Drug Discovery Lab, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy; [Florio, Rosalba; Verginelli, Fabio; Cama, Alessandro] Univ G dAnnunzio, Ctr Aging Sci & Translat Med CeSI MeT, Via Luigi Polacchi 11, I-66100 Chieti, Italy in 2019.0, Cited 30.0. SDS of cas: 104-10-9. The Name is 2-(4-Aminophenyl)ethanol. Through research, I have a further understanding and discovery of 104-10-9
The development of PPAR alpha/gamma dual or PPAR alpha/gamma/S pan-agonists could represent an efficacious approach for a simultaneous pharmacological intervention on carbohydrate and lipid metabolism. Two series of new phenyldiazenyl fibrate derivatives of GL479, a previously reported PPAR alpha/gamma dual agonist, were synthesized and tested. Compound 12a was identified as a PPAR pan-agonist with moderate and balanced activity on the three PPAR isoforms (alpha, gamma, delta). Moreover, docking experiments showed that 12a adopts a different binding mode in PPARy compared to PPARa or PPARS, providing a structural basis for further structure-guided design of PPAR pan-agonists. The beneficial effects of 12a were evaluated both in vitro, on the expression of PPAR target key metabolic genes, and ex vivo in two rat tissue inflammatory models. The obtained results allow considering this compound as an interesting lead for the development of a new class of PPAR pan-agonists endowed with an activation profile exploitable for therapy of metabolic syndrome.
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