Recent Progress in CDK4/6 Inhibitors and PROTACs

Molecules. 2023 Dec 13;28(24):8060. doi: 10.3390/molecules28248060.

Abstract

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.

Keywords: CDK4/6 inhibitors; PROTACs; cancer; cell cycle.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6*
  • Female
  • Humans
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proteolysis

Substances

  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Protein Kinase Inhibitors
  • CDK4 protein, human