An updated patent review of calpain inhibitors (2012 - 2014)

Expert Opin Ther Pat. 2015 Jan;25(1):17-31. doi: 10.1517/13543776.2014.982534. Epub 2014 Nov 15.


Introduction: Calpain is a family of cysteine proteases found in eukaryotes and a few bacteria. There is considerable interest in the search for calpain inhibitors because the enzyme has been implicated in several diseases including ocular disorders, neurodegenerative disorders, metabolic disorders and cancer.

Areas covered: An overview of calpain inhibitors disclosed between 2012 and 2014 is presented. Among these are epoxysuccinates, dipeptide imaging agents, macrocyclic inhibitors, α-helical peptidomimetic inhibitors, carboxamides, 5-azolones and α-mercaptoacrylates. Additionally, preclinical studies of calpain inhibitors in pathologies such blood disorders, ocular disorders, neurological disorders and muscle disorders are discussed.

Expert opinion: Major advances made in calpain inhibitor research between 2012 and 2014 include: i) the discovery of cytosolic-stable carboxamide calpain inhibitors; ii) synthesis of epoxysuccinates with excellent bioavailability; iii) disclosure of the X-ray crystal structures of novel α-mercaptoacrylates bound to the pentaEF hand region from human calpain; and iv) disclosure of calpain inhibitors as anti-sickling agents. Several calpain inhibitors were reported but limited effort was directed towards the discovery of calpain isoform selective agents, which continues to dampen the therapeutic potential of calpain inhibitors.

Keywords: calpain inhibitors; carboxamides; cataracts; epoxysuccinates; imaging agents; macrocycles; muscular dystrophy; peptidomimetics; sickle-cell disease; α-mercaptoacrylates.

Publication types

  • Review

MeSH terms

  • Animals
  • Calpain / antagonists & inhibitors*
  • Calpain / chemistry
  • Calpain / metabolism
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Cysteine Proteinase Inhibitors / therapeutic use
  • Drug Design
  • Drug Industry / legislation & jurisprudence*
  • Humans
  • Molecular Structure
  • Patents as Topic*
  • Peptides / pharmacology
  • Peptidomimetics / pharmacology
  • Protein Conformation
  • Structure-Activity Relationship


  • Cysteine Proteinase Inhibitors
  • Peptides
  • Peptidomimetics
  • Calpain