Linked Life Data

14965288

Source:http://linkedlifedata.com/resource/pubmed/id/14965288

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-17
pubmed:abstractText
Programmed cell death, or apoptosis, is executed by a series of Cysteine Aspartyl Proteases (Caspases) that form a proteolytic cascade. Each caspase functions either to activate downstream caspases by proteolytic cleavage and/or to proteolytically cleave cellular substrates. Increased levels of apoptosis and caspase activity are frequently observed at sites of cellular damage in both acute (e.g. myocardial infarction, stroke, sepsis) and chronic (e.g. Alzheimer's, Parkinson's and Huntington's Disease) indications. Thus, inhibition of caspase activity with the aim of reducing cell death, and hence tissue damage, is predicted to be therapeutically beneficial. Herein we outline different approaches that have been taken to identify small-molecule caspase inhibitors that include both traditional (e.g. HTS, structure-based design and substrate analog approaches) and novel screening technologies (e.g. Tethering). In addition, the characterization of inhibitors emerging from these programs will also be presented. Many of these compounds demonstrate efficacy in a wide range of animal models; however, only two examples of caspase inhibitors have progressed to clinical testing. Here we will discuss issues (both compound and mechanism related) associated with developing a caspase program in the pharmaceutical industry.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1389-5575
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-65
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Prospects for caspase inhibitors.
pubmed:affiliation
Sunesis Pharmaceuticals, Inc., 341 Oyster Point Blvd, South San Francisco, CA 94080, USA. tom@sunesis.com
pubmed:publicationType
Journal Article, Review