Recent Advances in IRAK1: Pharmacological and Therapeutic Aspects

Molecules. 2024 May 9;29(10):2226. doi: 10.3390/molecules29102226.

Abstract

Interleukin receptor-associated kinase (IRAK) proteins are pivotal in interleukin-1 and Toll-like receptor-mediated signaling pathways. They play essential roles in innate immunity and inflammation. This review analyzes and discusses the physiological functions of IRAK1 and its associated diseases. IRAK1 is involved in a wide range of diseases such as dry eye, which highlights its potential as a therapeutic target under various conditions. Various IRAK1 inhibitors, including Pacritinib and Rosoxacin, show therapeutic potential against malignancies and inflammatory diseases. The covalent IRAK1 inhibitor JH-X-119-01 shows promise in B-cell lymphomas, emphasizing the significance of covalent bonds in its activity. Additionally, the emergence of selective IRAK1 degraders, such as JNJ-101, provides a novel strategy by targeting the scaffolding function of IRAK1. Thus, the evolving landscape of IRAK1-targeted approaches provides promising avenues for increasingly safe and effective therapeutic interventions for various diseases.

Keywords: degrader; immunity; inhibitor; interleukin receptor-associated kinase (IRAK) proteins.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-1 Receptor-Associated Kinases* / antagonists & inhibitors
  • Interleukin-1 Receptor-Associated Kinases* / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Interleukin-1 Receptor-Associated Kinases
  • IRAK1 protein, human
  • Protein Kinase Inhibitors