The Arylhydrocarbon Receptor (AhR), a member of the Per-ARNT-SIM transcription factor family, has been as a potential new target to treat breast cancer sufferers. A series of 2-phenylacrylonitriles targeting AhR has been developed that have shown promising and selective activity against cancerous cell lines while sparing normal non-cancerous cells. A quantitative structure–activity relationship (QSAR) modeling approach was pursued in order to generate a predictive model for cytotoxicity to support ongoing synthetic activities and provide important structure-activity information for new structure design. Recent work conducted by us has identified a number of compounds that exhibited false positive cytotoxicity values in the standard MTT assay. This work describes a good quality model that not only predicts the activity of compounds in the MCF-7 breast cancer cell line, but was also able to identify structures that subsequently gave false positive values in the MTT assay by identifying compounds with aberrant biological behavior. This work not only allows the design of future breast cancer cytotoxic activity in vitro, but allows the avoidance of the synthesis of those compounds anticipated to result in anomalous cytotoxic behavior, greatly enhancing the design of such compounds.

芳烃受体 (AhR) 是 Per-ARNT-SIM 转录因子家族的成员，已成为治疗乳腺癌患者的潜在新靶点。已经开发了一系列针对 AhR 的 2-苯基丙烯腈，它们显示出对癌细胞系的有希望的选择性活性，同时保留了正常的非癌细胞。采用定量构效关系 (QSAR) 建模方法，以生成细胞毒性预测模型，以支持正在进行的合成活动，并为新的结构设计提供重要的构效信息。我们最近进行的工作已经确定了许多在标准 MTT 测定中表现出假阳性细胞毒性值的化合物。这项工作描述了一个高质量的模型，它不仅可以预测 MCF-7 乳腺癌细胞系中化合物的活性，而且还能够通过识别具有异常生物学行为的化合物来识别随后在 MTT 测定中给出假阳性值的结构。这项工作不仅允许在体外设计未来的乳腺癌细胞毒活性，而且可以避免合成那些预期会导致异常细胞毒行为的化合物，从而大大增强了此类化合物的设计。