A survey of calpain inhibitors

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Calpain is unique among the cysteine protease family of enzymes in that it combines thiol protease activity with calmodulin-like activity. Despite its wide spread distribution the exact physiological function(s) of calpain is yet to be deciphered. The enzyme is however, implicated in a number of pathophysiological conditions. Due to the potential of calpain as a therapeutic target a number of inhibitors have been described for the enzyme. In this article we have grouped calpain inhibitors into those derived from natural sources, and those derived from chemical synthesis. Additionally, an overview of functional groups that have been used as 'warheads' of calpain inhibitors is presented along with a discussion of the structure activity relationship studies of the address region of peptidyl calpain inhibitors. Recent work in this area has led to a better understanding of the structural requirements for tight binding of inhibitors to the active site of calpain. A discussion of peptidomimetic calpain inhibitors, nonpeptide calpain inhibitors, and selectivity of some calpain inhibitors are also presented. The recent disclosure of the crystal structure of a nonpeptide calpain inhibitor bound to a hydrophobic pocket on the calcium-binding domain of calpain has opened the door to future development of potent cell permeable nonpeptide calpain inhibitors.

Original languageEnglish (US)
Pages (from-to)1171-1188
Number of pages18
JournalCurrent Medicinal Chemistry
Volume7
Issue number12
DOIs
StatePublished - Jan 1 2000

Fingerprint

Calpain
Enzymes
Peptidomimetics
Cysteine Proteases
Surveys and Questionnaires
calpain inhibitors
Disclosure
Calmodulin
Structure-Activity Relationship
Sulfhydryl Compounds
Functional groups
Catalytic Domain
Peptide Hydrolases
Crystal structure
Calcium

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

A survey of calpain inhibitors. / Donkor, Isaac.

In: Current Medicinal Chemistry, Vol. 7, No. 12, 01.01.2000, p. 1171-1188.

Research output: Contribution to journalArticle

Donkor, Isaac. / A survey of calpain inhibitors. In: Current Medicinal Chemistry. 2000 ; Vol. 7, No. 12. pp. 1171-1188.
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