Structural insights into Estrogen Related Receptor-β modulation: 4-methylenesterols from Theonella swinhoei sponge as the first example of marine natural antagonists.

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.