Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery

被引：37

作者：

Martin, Ryan D. ^{[1
]}

Hebert, Terence E. ^{[1
]}

Tanny, Jason C. ^{[1
]}

机构：

[1] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 09期

基金：

加拿大健康研究院;

关键词：

RNA polymerase II; transcription; CDK inhibitor; CDK7; CDK9; CDK12; CYCLIN-DEPENDENT KINASE; CONTINUOUS-INFUSION FLAVOPIRIDOL; DINACICLIB SCH 727965; STRUCTURAL BASIS; PHASE-II; P-TEFB; INHIBITOR FLAVOPIRIDOL; IN-VIVO; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY;

D O I：

10.3390/ijms21093354

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：24

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