|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2010-5-3
|
|
pubmed:abstractText |
Herein, we examine the potential of a nitrile-containing propionic acid moiety as an electrophile for covalent attack by the active-site cysteine residue of caspase 1. The syntheses of several cyanopropanate-containing small molecules based on the optimized peptidic scaffold of prodrug VX-765 were accomplished. These compounds were found to be potent inhibitors of caspase 1 (IC(50) values < or =1 nM). Examination of these novel small molecules against a caspase panel demonstrated an impressive degree of selectivity for caspase 1 inhibition over other caspase isozymes. Assessment of hydrolytic stability and selected ADME properties highlighted these agents as potentially useful tools for studying caspase 1 down-regulation in various settings, including in vivo analyses.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-10872455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-11141092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-12133721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-12475198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-15163405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-15296730,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-16375749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-16611146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-16984172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-17157022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-17289835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-18081302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-18173229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-18298652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-18779046,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-19221555,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-7619812,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-8035875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20229566-9987822
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1860-7187
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
3
|
|
pubmed:volume |
5
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
730-8
|
|
pubmed:dateRevised |
2011-7-26
|
|
pubmed:meshHeading |
pubmed-meshheading:20229566-4-Aminobenzoic Acid,
pubmed-meshheading:20229566-Animals,
pubmed-meshheading:20229566-Binding Sites,
pubmed-meshheading:20229566-Caspase 1,
pubmed-meshheading:20229566-Catalytic Domain,
pubmed-meshheading:20229566-Computer Simulation,
pubmed-meshheading:20229566-Cysteine Proteinase Inhibitors,
pubmed-meshheading:20229566-Dipeptides,
pubmed-meshheading:20229566-Humans,
pubmed-meshheading:20229566-Microsomes, Liver,
pubmed-meshheading:20229566-Propionic Acids,
pubmed-meshheading:20229566-Rats,
pubmed-meshheading:20229566-Structure-Activity Relationship
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety.
|
|
pubmed:affiliation |
National Institutes of Health, National Human Genome Research Institute, NIH Chemical Genomics Center, Rockville, Maryland 20850, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
|
