Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy

J Med Chem. 2016 Oct 13;59(19):8667-8684. doi: 10.1021/acs.jmedchem.6b00150. Epub 2016 Jun 3.

Abstract

Cyclin dependent kinase (CDK) inhibitors have been the topic of intense research for nearly 2 decades due to their widely varied and critical functions within the cell. Recently CDK9 has emerged as a druggable target for the development of cancer therapeutics. CDK9 plays a crucial role in transcription regulation; specifically, CDK9 mediated transcriptional regulation of short-lived antiapoptotic proteins is critical for the survival of transformed cells. Focused chemical libraries based on a plethora of scaffolds have resulted in mixed success with regard to the development of selective CDK9 inhibitors. Here we review the regulation of CDK9, its cellular functions, and common core structures used to target CDK9, along with their selectivity profile and efficacy in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 9 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 9 / chemistry
  • Cyclin-Dependent Kinase 9 / metabolism
  • Drug Discovery / methods*
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Humans
  • Macrocyclic Compounds / chemistry
  • Macrocyclic Compounds / pharmacology
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Purines / chemistry
  • Purines / pharmacology
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Triazines / chemistry
  • Triazines / pharmacology

Substances

  • Flavonoids
  • Macrocyclic Compounds
  • Protein Kinase Inhibitors
  • Purines
  • Pyrazoles
  • Pyrimidines
  • Triazines
  • Cyclin-Dependent Kinase 9