Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure–activity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2,3-triazoles as novel suppressors of ERRα transcriptional functions. The most promising compound, 2-aminophenyl-(1-(3-isopropylphenyl)-1H-1,2,3-triazol-4-yl)methanone (14n), potently suppressed the transcriptional functions of ERRα with IC₅₀ = 0.021 μM in a cell-based reporter gene assay and also decreased both the mRNA levels and the protein levels of ERRα and the downstream targets. This compound inhibited the proliferation and migration of breast cancer cells with high level of ERRα. Preliminary pharmacokinetic studies suggested that it possessed a good pharmacokinetic profile with an oral bioavailability of 71.8%. The compounds may serve as novel small molecule probes for further validation of ERRα as a molecular target for anticancer drug development.

中文翻译：

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1-苯基-4-苯甲酰基-1 H -1,2,3-三唑作为雌激素相关受体α的口服生物利用转录功能抑制剂

雌激素相关受体α是治疗乳腺癌的潜在候选靶标。我们描述了一系列的1-苯基-4-苯甲酰基-1 H -1,2,3-三唑作为ERRα转录功能的新型抑制剂的发现和构效关系研究。最有前途的化合物2-氨基苯基-（1-（3-异丙基苯基）-1 H -1,2,3-三唑-4-基）甲酮（14n）用IC ₅₀有效抑制ERRα的转录功能在基于细胞的报告基因分析中，DNA含量= 0.021μM，并且还降低了ERRα和下游靶标的mRNA水平和蛋白质水平。该化合物抑制具有高ERRα水平的乳腺癌细胞的增殖和迁移。初步的药代动力学研究表明，它具有良好的药代动力学特征，口服生物利用度为71.8％。该化合物可作为新型小分子探针，用于进一步验证ERRα作为抗癌药物开发的分子靶标。