A patent review of MAPK inhibitors (2018 - present)

Expert Opin Ther Pat. 2023 Jan-Jun;33(6):421-444. doi: 10.1080/13543776.2023.2242584. Epub 2023 Aug 1.

Abstract

Introduction: The mitogen-activated protein kinase (MAPK) family consist of p38 MAP kinases, c-Jun N-terminal kinases (JNKs) and extracellular signal-regulated kinases (ERKs). They are involved in a multitude of diseases, including inflammatory, autoimmune, neurodegenerative, and metabolic diseases as well as cancer. In recent years, further developments in the field of MAPK-inhibitors have been reported, including an isoform or downstream target selective inhibition of MAPKs as well as target protein degradation approaches.

Areas covered: This review summarizes newly patented MAPK-inhibitors that were claimed between 2018 and early 2023. Presented are the patents as well as their corresponding publications, the storyline of development, and clinical trials involving these compounds. This article elaborates a total of 27 patents, which were identified using established search engines.

Expert opinion: Although industrial research on MAPK-inhibitors has been ongoing for more than 20 years, novel clinical trials of MAPK-inhibitors as potential drug candidates are still being conducted in the period under review. Recently reported inhibitors show an excellent selectivity profile and are even achieving selectivity between closely related isoforms. This progression offers the possibility to eliminate unwanted side effects and may finally lead to the approval of the first MAPK-inhibitor.

Keywords: C-Jun N-terminal kinase; P38 MAP kinase; deuteration; downstream target selectivity; extracellular signal-regulated kinase; isoform selectivity; mitogen-activated protein kinase; protacs.

Publication types

  • Review

MeSH terms

  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • JNK Mitogen-Activated Protein Kinases / pharmacology
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases* / metabolism
  • Mitogen-Activated Protein Kinases* / pharmacology
  • Patents as Topic*
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Mitogen-Activated Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Protein Kinase Inhibitors