Wiedemann Bianca, Weisner Jörn, Rauh Daniel
Technische Universität Dortmund , Fakultät für Chemie und Chemische Biologie , Otto-Hahn-Strasse 4a , D-44227 Dortmund , Germany . Email:
Medchemcomm. 2018 Jul 11;9(8):1249-1272. doi: 10.1039/c8md00273h. eCollection 2018 Aug 1.
Transcription factors (TFs) constitute a diverse class of sequence-specific DNA-binding proteins, which are key to the modulation of gene expression. TFs have been associated with human diseases, including cancer, Alzheimer's and other neurodegenerative diseases, which makes this class of proteins attractive targets for chemical biology and medicinal chemistry research. Since TFs lack a common binding site or structural similarity, the development of small molecules to efficiently modulate TF biology in cells and is a challenging task. This review highlights various strategies that are currently being explored for the identification and development of modulators of Myc, p53, Stat, Nrf2, CREB, ER, AR, HIF, NF-κB, and BET proteins.
转录因子(TFs)构成了一类多样的序列特异性DNA结合蛋白,它们是调节基因表达的关键。转录因子与包括癌症、阿尔茨海默病和其他神经退行性疾病在内的人类疾病相关,这使得这类蛋白质成为化学生物学和药物化学研究的有吸引力的靶点。由于转录因子缺乏共同的结合位点或结构相似性,开发能够有效调节细胞中转录因子生物学功能的小分子是一项具有挑战性的任务。本综述重点介绍了目前正在探索的用于鉴定和开发Myc、p53、Stat、Nrf2、CREB、雌激素受体(ER)、雄激素受体(AR)、缺氧诱导因子(HIF)、核因子κB(NF-κB)和溴结构域和额外末端结构域(BET)蛋白调节剂的各种策略。