The latest perspectives of small molecules FMS kinase inhibitors

Eur J Med Chem. 2023 Dec 5:261:115796. doi: 10.1016/j.ejmech.2023.115796. Epub 2023 Sep 7.

Abstract

FMS kinase is a type III tyrosine kinase receptor that plays a central role in the pathophysiology and management of several diseases, including a range of cancer types, inflammatory disorders, neurodegenerative disorders, and bone disorders among others. In this review, the pathophysiological pathways of FMS kinase in different diseases and the recent developments of its monoclonal antibodies and inhibitors during the last five years are discussed. The biological and biochemical features of these inhibitors, including binding interactions, structure-activity relationships (SAR), selectivity, and potencies are discussed. The focus of this article is on the compounds that are promising leads and undergoing advanced clinical investigations, as well as on those that received FDA approval. In this article, we attempt to classify the reviewed FMS inhibitors according to their core chemical structure including pyridine, pyrrolopyridine, pyrazolopyridine, quinoline, and pyrimidine derivatives.

Keywords: Anti-inflammatory; Anticancer; CSF-1R; FMS antibody; FMS inhibitor; Microglia.

Publication types

  • Review

MeSH terms

  • Humans
  • Neoplasms*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Structure-Activity Relationship

Substances

  • Receptor Protein-Tyrosine Kinases