Abstract
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.
Keywords:
CDK inhibitor; CDK12; CDK7; CDK9; RNA polymerase II; transcription.
MeSH terms
-
Antineoplastic Agents / pharmacology*
-
Catalysis / drug effects
-
Clinical Trials as Topic
-
Cyclin-Dependent Kinase 8 / antagonists & inhibitors
-
Cyclin-Dependent Kinase 9 / antagonists & inhibitors
-
Cyclin-Dependent Kinases / antagonists & inhibitors*
-
Drug Screening Assays, Antitumor
-
Gene Expression Regulation, Neoplastic / drug effects*
-
Humans
-
Molecular Targeted Therapy*
-
Neoplasm Proteins / antagonists & inhibitors*
-
Neoplasm Proteins / physiology
-
Neoplasms / drug therapy*
-
Neoplasms / enzymology
-
Protein Kinase Inhibitors / pharmacology
-
Protein Kinase Inhibitors / therapeutic use
-
RNA Polymerase II / drug effects*
-
RNA Polymerase II / physiology
-
Transcription, Genetic / drug effects*
Substances
-
Antineoplastic Agents
-
Neoplasm Proteins
-
Protein Kinase Inhibitors
-
CDK8 protein, human
-
CDK9 protein, human
-
Cyclin-Dependent Kinase 8
-
Cyclin-Dependent Kinase 9
-
Cyclin-Dependent Kinases
-
RNA Polymerase II