The journey of p38 MAP kinase inhibitors: From bench to bedside in treating inflammatory diseases

Eur J Med Chem. 2024 Dec 15:280:116950. doi: 10.1016/j.ejmech.2024.116950. Epub 2024 Oct 11.

Abstract

The p38 mitogen-activated protein kinase (MAPK) pathway is pivotal in regulating inflammatory responses and has emerged as a key target for the development of small-molecule inhibitors aimed at treating inflammatory diseases. In arthritis, especially rheumatoid arthritis (RA), the p38 MAPK pathway contributes to chronic inflammation and joint destruction by promoting the production of pro-inflammatory cytokines. Preclinical studies have shown that small-molecule inhibitors targeting the p38 MAPK pathway hold significant promise, exhibiting the potential to reduce inflammation and preserve joint integrity. Targeting this pathway presents a novel therapeutic approach to mitigating inflammation. This review traces the evolution of p38 MAP kinase inhibitors from initial laboratory studies to clinical candidates, underscoring their potential to significantly alter the treatment approach for inflammatory diseases.

Keywords: Clinical trials; Inflammation; MAPK; p38 MAP inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Humans
  • Inflammation* / drug therapy
  • Molecular Structure
  • Protein Kinase Inhibitors* / chemical synthesis
  • Protein Kinase Inhibitors* / chemistry
  • Protein Kinase Inhibitors* / pharmacology
  • Protein Kinase Inhibitors* / therapeutic use
  • p38 Mitogen-Activated Protein Kinases* / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases
  • Protein Kinase Inhibitors
  • Anti-Inflammatory Agents