Peptidylarginine deiminases 4 as a promising target in drug discovery

Eur J Med Chem. 2021 Dec 15:226:113840. doi: 10.1016/j.ejmech.2021.113840. Epub 2021 Sep 9.

Abstract

Peptidylarginine deaminase 4 (PAD4) is a crucial post-translational modifying enzyme catalyzing the conversion of arginine into citrulline residues, and mediating the formation of neutrophil extracellular traps (NETs). PAD4 plays a vital role in the occurrence and development of cardiovascular diseases, autoimmune diseases, and various tumors. Therefore, PAD4 is considered as a promising drug target for disease diagnosis and treatment. More and more efforts are devoted to developing highly efficient and selective PAD4 inhibitors via high-throughput screening, structure-based drug design and structure-activity relationship study. This article outlined the physiological and pathological functions of PAD4, and corresponding representative small molecule inhibitors reported in recent years.

Keywords: Autoimmune disease; Citrullination; Histone; NETs; PAD4 inhibitor.

Publication types

  • Review

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Protein-Arginine Deiminase Type 4 / antagonists & inhibitors*
  • Protein-Arginine Deiminase Type 4 / chemistry
  • Protein-Arginine Deiminase Type 4 / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • PADI4 protein, human
  • Protein-Arginine Deiminase Type 4