RIPK2 inhibitors for disease therapy: Current status and perspectives

Eur J Med Chem. 2023 Nov 5:259:115683. doi: 10.1016/j.ejmech.2023.115683. Epub 2023 Jul 26.

Abstract

Receptor-interacting protein kinase 2 (RIPK2) belongs to the receptor-interacting protein family (RIPs), which is mainly distributed in the cytoplasm. RIPK2 is widely expressed in human tissues, and its mRNA level is highly expressed in the spleen, leukocytes, placenta, testis, and heart. RIPK2 is a dual-specificity kinase with multiple domains, which can interact with tumor necrosis factor receptor (TNFR), and participate in the Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD) signaling pathways. It is considered as a vital adapter molecule involved in the innate immunity, adaptive immunity, and apoptosis. Functionally, RIPK2 and its targeted small molecules are of great significance in inflammatory responses, autoimmune diseases and tumors. The present study reviews the molecule structure and biological functions of RIPK2, and its correlation between human diseases. In addition, we focus on the structure-activity relationship of small molecule inhibitors of RIPK2 and their therapeutic potential in human diseases.

Keywords: Drug design; Immunity; RIPK2; RIPK2 inhibitors; Structure activity relationship.

Publication types

  • Review

MeSH terms

  • Humans
  • Immunity, Innate*
  • Male
  • Protein Kinase Inhibitors* / chemistry
  • Protein Kinase Inhibitors* / pharmacology
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / antagonists & inhibitors
  • Signal Transduction*
  • Toll-Like Receptors

Substances

  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • RIPK2 protein, human
  • Toll-Like Receptors
  • Protein Kinase Inhibitors