The BET family proteins play pleiotropic roles in the tumorigenesis and growth of various human malignancies that have aroused great interests as the cancer therapeutic targets. Therefore, it's significant to develop labeling toolkits for the dynamic monitoring of BET family proteins in living tumor cells and tissue slices. In particular, there are few small-molecule fluorescent probes based on BET family proteins developed for real-time imaging of these proteins in tumor cells and tissues and treatment of breast cancer. In general, antibodies of BET family proteins are chosen for imaging of these proteins. However, the cost of these antibodies is more expensive than small molecules and the operation is relatively complicated. Moreover, the antibodies for imaging are not capable of the therapy for breast cancer. Thus, it's essential to exploit a novel imaging system for BET family proteins which is easy-operating and economical, with achieving therapeutic effects simultaneously. Therefore, a series of fluorescent probes (17–21) targeting BET family proteins were developed. Through the evaluation studies, probe 17 showed advantages in docking studies, analysis of cell viability, and imaging studies. Importantly, probe 17 was capable of distinguishing tumor cells and tissue slices and made a distinction between them by labeling BRD3 and BRD4 proteins. Importantly, probe 17 showed higher resolution in mouse tumor and human tumor slice imaging than BRD3 and BRD4 antibodies. Moreover, compared with these antibodies, probe 17 was more stable, more economical and easier to operate in the imaging assays. In addition, it also played an anti-tumor role by inducing cell apoptosis, proliferation inhibition, and cycle arrest in tumor cells. All these features render probe 17 to perform as an effective labeling toolkit compatible for imaging studies of BRD3/BRD4, as well as an approach to diagnosis and treatment of breast cancer.

中文翻译：

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实现靶向 BRD3/BRD4 的治疗诊断探针，用于肿瘤成像和治疗


BET 家族蛋白在各种人类恶性肿瘤的肿瘤发生和生长中起多效性作用，作为癌症治疗靶点引起了人们的极大兴趣。因此，开发用于动态监测活肿瘤细胞和组织切片中 BET 家族蛋白的标记工具包具有重要意义。特别是，很少有基于 BET 家族蛋白的小分子荧光探针被开发用于肿瘤细胞和组织中这些蛋白质的实时成像以及乳腺癌的治疗。通常，选择 BET 家族蛋白的抗体用于这些蛋白质的成像。然而，这些抗体的成本比小分子抗体更昂贵，而且操作相对复杂。此外，用于成像的抗体不能用于治疗乳腺癌。因此，必须开发一种新型的 BET 家族蛋白成像系统，该系统易于操作且经济，同时能达到治疗效果。因此，开发了一系列靶向 BET 家族蛋白的荧光探针 （17–21）。通过评价研究，探针 17 在对接研究、细胞活力分析和影像学研究方面显示出优势。重要的是，探针 17 能够区分肿瘤细胞和组织切片，并通过标记 BRD3 和 BRD4 蛋白来区分它们。重要的是，探针 17 在小鼠肿瘤和人肿瘤切片成像中显示出比 BRD3 和 BRD4 抗体更高的分辨率。此外，与这些抗体相比，探针 17 在成像分析中更稳定、更经济、更易于操作。此外，它还通过诱导肿瘤细胞凋亡、增殖抑制和周期停滞发挥抗肿瘤作用。 所有这些功能使探针 17 成为一种有效的标记工具包，与 BRD3/BRD4 的成像研究以及乳腺癌的诊断和治疗方法兼容。