title: Calpain inhibitors: a survey of compounds reported in the patent and scientific literature.
abstract: BACKGROUND
  Calpain is a cysteine protease that participates in normal signal transduction events, but deregulation of its action may result in pathologies such as neurological disorders, muscular dystrophies, cataract, cancer and diabetes. Inhibition of calpain is demonstrably beneficial in animal models of these diseases; hence, the enzyme has been proposed as a potential drug target.
  
  
  METHODS
  A comprehensive review of calpain inhibitors reported in the patent and scientific literature over the past decade (2001 - 2010) is presented in this paper. Peptides, peptidomimetics and nonpeptide inhibitors with and without reactive warheads are discussed. Advances made in enhancing the cellular uptake of peptide calpain inhibitors, improving the pharmacokinetic properties of the inhibitors and site specific targeting of calpain inhibitors are also discussed.
  
  
  CONCLUSIONS
  Calpain inhibitors have demonstrated efficacy in animal models of calpain related diseases, but progression of the inhibitors into clinical trials has been hampered partly due to lack of calpain isoform selectivity and the general reactivity of the inhibitors. Therefore, efforts should be directed towards the discovery of compounds devoid of these problems. Exploration of compounds that bind to allosteric sites of the enzyme may circumvent these problems and afford new drug leads.
authors: The University of Tennessee Health Science Center, College of Pharmacy, Department of Pharmaceutical Sciences, 847 Monroe Avenue, 327E Johnson Building, Memphis, TN 38163, USA. idonkor@uthsc.edu
authors: Isaac O
authors: IO
authors: Donkor
mesh_terms: D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D002867:Chromones / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D010330:Patents as Topic; D057786:Peptidomimetics / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002867:Chromones; D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D057786:Peptidomimetics; D002154:Calpain