Discerning the promising binding sites of S100/calgranulins and their therapeutic potential in atherosclerosis

Expert Opin Ther Pat. 2021 Nov;31(11):1045-1057. doi: 10.1080/13543776.2021.1937122. Epub 2021 Jun 10.

Abstract

Introduction: Atherosclerosis is a chronic inflammatory disease in which the members of S100 family proteins (calgranulins) bind with their receptors, particularly receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4) and play a key role in the pathogenesis and progression of disease. Thus, these proteins could be considered as potential biomarkers and therapeutic targets in the treatment of atherosclerotic inflammation.

Areas covered: This review summarizes the pathology of S100A8, S100A9, and S100A12 in the development of atherosclerosis and reveals key structural features of these proteins which are potentially critical in their pathological effects. This article focuses on the translational significance of antagonizing these proteins by using small molecules in patent literature, clinical and preclinical studies and also discusses future approaches that could be employed to block these proteins in the treatment of atherosclerosis.

Expert opinion: Based on the critical role of S100/calgranulins in the regulation of atherosclerosis, these proteins are potential targets to develop better therapeutic options in the treatment of inflammatory diseases. However, further research is still needed to clarify their exact molecular mechanism by analyzing their detailed structural features that can expedite future research to develop novel therapeutics against these proteins to treat atherosclerotic inflammation.

Keywords: Atherosclerosis; calgranulins; rage; s100a12; s100a8; s100a9; toll-like receptor-4.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • Binding Sites
  • Biomarkers / metabolism
  • Calgranulin A / metabolism
  • Calgranulin B / metabolism
  • Drug Development*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Leukocyte L1 Antigen Complex / metabolism
  • Patents as Topic
  • S100A12 Protein / metabolism

Substances

  • Biomarkers
  • Calgranulin A
  • Calgranulin B
  • Leukocyte L1 Antigen Complex
  • S100A12 Protein
  • S100A12 protein, human
  • S100A8 protein, human
  • S100A9 protein, human