Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
Int J Mol Sci. 2020 May 9;21(9):3354. doi: 10.3390/ijms21093354.
Inhibitors targeting the general RNA polymerase II (RNAPII) transcription machinery are candidate therapeutics in cancer and other complex diseases. Here, we review the molecular targets and mechanisms of action of these compounds, framing them within the steps of RNAPII transcription. We discuss the effects of transcription inhibitors in vitro and in cellular models (with an emphasis on cancer), as well as their efficacy in preclinical and clinical studies. We also discuss the rationale for inhibiting broadly acting transcriptional regulators or RNAPII itself in complex diseases.
靶向通用 RNA 聚合酶 II（RNAPII）转录机制的抑制剂是癌症和其他复杂疾病的候选治疗药物。在这里，我们回顾了这些化合物的分子靶标和作用机制，将它们框定在 RNAPII 转录的步骤内。我们讨论了转录抑制剂在体外和细胞模型中的作用（重点是癌症），以及它们在临床前和临床研究中的疗效。我们还讨论了在复杂疾病中抑制广泛作用的转录调节剂或 RNAPII 本身的原理。
