title: The potential for caspases in drug discovery.
abstract: 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.affiliation: North Carolina State University, Department of Molecular and Structural Biochemistry, 128 Polk Hall, Raleigh, NC 27695, USA.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: MacKenzie
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Schipper
authors.forename: A Clay
authors.initials: AC
authors.lastname: Clark
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D055808:Drug Discovery / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D057786:Peptidomimetics; D054852:Small Molecule Libraries; D020169:Caspases
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