title: Structural insights into Estrogen Related Receptor-β modulation: 4-methylenesterols from Theonella swinhoei sponge as the first example of marine natural antagonists.
abstract: In this paper, we report the first evidence of 4-methylenesterols, isolated from the marine sponge Theonella swinhoei, as antagonists of Estrogen Related Receptors (ERRs). The interactions of 4-methylenesterols with ERRs were investigated through a multi-parametric approach involving biological assays and molecular modelling. Here the first homology model of active and inactive conformations of the Estrogen Related Receptor β (ERRβ) is also reported, benchmarked with the well known agonists gsk4716 and genistein, and the antagonists 4-hydroxytamoxifen and diethylstilbestrol. Our proposed model could contribute to the clarification of small molecule interaction mode in the ERRβ and, notably, to the rational design of new potential and selective modulators of this emerging therapeutic target.
authors: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
authors: Simone
authors: S
authors: Di Micco
authors: Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Nuova Facoltà di Medicina e Chirurgia, Via Gerardo Dottori 1 S. Andrea delle Fratte, 06132 Perugia, Italy.
authors: Barbara
authors: B
authors: Renga
authors: Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Nuova Facoltà di Medicina e Chirurgia, Via Gerardo Dottori 1 S. Andrea delle Fratte, 06132 Perugia, Italy.
authors: Adriana
authors: A
authors: Carino
authors: Dipartimento di Farmacia, Università degli Studi di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors: Maria Valeria
authors: MV
authors: D'Auria
authors: Dipartimento di Farmacia, Università degli Studi di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors: Angela
authors: A
authors: Zampella
authors: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
authors: Raffaele
authors: R
authors: Riccio
authors: Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Nuova Facoltà di Medicina e Chirurgia, Via Gerardo Dottori 1 S. Andrea delle Fratte, 06132 Perugia, Italy.
authors: Stefano
authors: S
authors: Fiorucci
authors: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy. Electronic address: bifulco@unisa.it.
authors: Giuseppe
authors: G
authors: Bifulco
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors*; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D047232:Theonella / Q000737:chemistry*
chemical_list: D001688:Biological Products; D047629:Estrogen Receptor beta; D013256:Steroids
keywords: Cancer; ERR ligand; Estrogen Related Receptor α; Estrogen Related Receptor β; Estrogen Related Receptor γ; Metabolic disorders