Document Detail


The potential for caspases in drug discovery.
MedLine Citation:
PMID:  20812148     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caspases are a family of proteases that are involved in the execution of apoptosis and the inflammatory response. A plethora of diseases occur as a result of the dysregulation of apoptosis and inflammation, and caspases have been targeted as a therapeutic strategy to halt the progression of such diseases. Hundreds of peptide and peptidomimetic inhibitors have been designed and tested, but only a few have advanced to clinical trials because of poor drug-like properties and pharmacological constraints. Although much effort has been focused on inhibiting caspases, there are many diseases that result from a decrease in apoptosis, thus activating procaspases could also be a viable therapeutic strategy. To this end, recent efforts have focused on the design of procaspase-3 activators. This review highlights the current progress in the rational design of both specific and pan-caspase inhibitors, as well as procaspase-3 activators.
Authors:
Sarah H MacKenzie; Joshua L Schipper; A Clay Clark
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current opinion in drug discovery & development     Volume:  13     ISSN:  2040-3437     ISO Abbreviation:  Curr Opin Drug Discov Devel     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2011-01-18     Revised Date:  2012-02-29    
Medline Journal Info:
Nlm Unique ID:  100887519     Medline TA:  Curr Opin Drug Discov Devel     Country:  England    
Other Details:
Languages:  eng     Pagination:  568-76     Citation Subset:  IM    
Affiliation:
North Carolina State University, Department of Molecular and Structural Biochemistry, 128 Polk Hall, Raleigh, NC 27695, USA.
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MeSH Terms
Descriptor/Qualifier:
Allosteric Regulation
Allosteric Site
Animals
Apoptosis / drug effects
Caspases / antagonists & inhibitors,  metabolism*
Drug Discovery / methods*
Enzyme Activation / drug effects
Enzyme Inhibitors / chemistry,  pharmacology*
Humans
Models, Molecular
Molecular Structure
Peptidomimetics / chemistry,  pharmacology*
Small Molecule Libraries / chemistry,  pharmacology*
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
R01 GM065970-07/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Peptidomimetics; 0/Small Molecule Libraries; EC 3.4.22.-/Caspases

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