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


METHODS
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.


CONCLUSIONS
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.
The University of Tennessee Health Science Center , Memphis, TN , USA idonkor@uthsc.edu.
Isaac O
IO
Donkor
D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004345:Drug Industry / Q000331:legislation & jurisprudence*; D006801:Humans; D015394:Molecular Structure; D010330:Patents as Topic; D010455:Peptides / Q000494:pharmacology; D057786:Peptidomimetics / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D057786:Peptidomimetics; D002154:Calpain
calpain inhibitors; carboxamides; cataracts; epoxysuccinates; imaging agents; macrocycles; muscular dystrophy; peptidomimetics; sickle-cell disease; α-mercaptoacrylates