A comprehensive insight on the recent development of Cyclic Dependent Kinase inhibitors as anticancer agents

Eur J Med Chem. 2020 Oct 1:203:112571. doi: 10.1016/j.ejmech.2020.112571. Epub 2020 Jul 15.

Abstract

Cancer is one of the major leading causes of death worldwide despite many breakthroughs in the development of novel anticancer drugs. The heterodimer CDK-Cyclin complex plays an essential role in regulating cellular processes. For example, epigenetics, neuronal activity, gene transcription, metabolism, DNA repair, angiogenesis, and hematopoiesis. Consequently, CDKs are often deregulated and over-expressed, causing an uncontrolled proliferation in tumors. Due to their active role in cell cycle regulation and transcription activity, CDKs are conceived as promising targets to overcome cell proliferation. Therefore, designing and developing efficient Cyclic Dependent Kinase inhibitors is progressively becoming a credible solution in treating cancers. This review article emphasized the recent developments of cyclic dependent Kinase inhibitors with insights into their structure-activity relationship, molecular docking, and mechanism of action.

Keywords: Anticancer hybrids; CDK inhibitors; Cancer; Covalent inhibitors; PROTACs; Transcriptional CDKs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Drug Discovery*
  • Humans
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Protein Kinases