To investigate androgen receptor (AR) activation by exogenous compounds, we used a combination of experimental analysis and theoretical modeling to compare a set of brominated flame retardants (BFRs) to dihydrotestosterone (DHT) with regard to ligand docking, AR binding, and AR activation in human hepatocellular liver carcinoma cells, as well as interacting energy analysis. Modeling of receptor docking was found to be a useful first step in predicting the potential to translocate to the ligand pocket of the receptor, and the computed interaction energy was found to correlate with the observed binding affinity. Flexible alignment studies of the BFR compounds demonstrated that 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (BCH) closely overlap DHT. Combining the theoretical modeling with in vitro ligand-binding and receptor-activation assays, we show that BCH binds to and activates the human AR. The remaining BFRs did not successfully interact with the ligand pocket, were not able to replace a synthetic androgen from the receptor, and failed to activate the receptor.

中文翻译：

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鉴定溴化阻燃剂1,2-二溴-4-（1,2-二溴乙基）环己烷为雄激素激动剂。

为了研究外源性化合物对雄激素受体（AR）的活化作用，我们结合了实验分析和理论模型，对配体对接，AR结合和AR活化方面的一组溴化阻燃剂（BFR）与二氢睾酮（DHT）进行了比较。在人类肝细胞肝癌细胞中的作用，以及相互作用的能量分析。发现受体对接的模型是预测转移到受体的配体口袋的潜力的有用的第一步，并且发现计算的相互作用能与观察到的结合亲和力相关。BFR化合物的灵活比对研究表明1,2-二溴-4-（1,2-二溴乙基）环己烷（BCH）与DHT紧密重叠。将理论模型与体外配体结合和受体激活测定相结合，我们证明BCH结合并激活了人类AR。其余的BFR无法与配体袋成功相互作用，无法取代受体合成的雄激素，也无法激活受体。