|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
1999-2-11
|
|
pubmed:abstractText |
A new series of hydroxamic acid-based matrix metalloproteinase (MMP) inhibitors containing a unique phosphinamide motif derived from D-amino acid was designed, synthesized, and tested for enzyme inhibition. Compounds with an R configuration at phosphorus were found to be potent MMP inhibitors while molecules with the S configuration were almost inactive. Structure-activity relationship studies of the series led to the discovery of the potent inhibitor 16 with IC50 = 20.5 nM and 24.4 nM against fibroblast collagenase (MMP-1) and stromelysin (MMP-3), respectively. The binding mode of this novel phosphinamide-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 16.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagenases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/MMP13 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 13,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 7,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
0022-2623
|
|
pubmed:author |
pubmed-author:AlmsteadN GNG,
pubmed-author:AnastasioM VMV,
pubmed-author:ChenLL,
pubmed-author:DunawayC MCM,
pubmed-author:EYWW,
pubmed-author:KAON CNC,
pubmed-author:McDow DunhamK LKL,
pubmed-author:McPhailS JSJ,
pubmed-author:MielingG EGE,
pubmed-author:NatchusM GMG,
pubmed-author:PikusJJ,
pubmed-author:SniderC ECE,
pubmed-author:TaiwoY OYO
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
14
|
|
pubmed:volume |
42
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
87-94
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:9888835-Binding Sites,
pubmed-meshheading:9888835-Collagenases,
pubmed-meshheading:9888835-Crystallography, X-Ray,
pubmed-meshheading:9888835-Drug Design,
pubmed-meshheading:9888835-Humans,
pubmed-meshheading:9888835-Hydroxamic Acids,
pubmed-meshheading:9888835-Matrix Metalloproteinase 1,
pubmed-meshheading:9888835-Matrix Metalloproteinase 13,
pubmed-meshheading:9888835-Matrix Metalloproteinase 3,
pubmed-meshheading:9888835-Matrix Metalloproteinase 7,
pubmed-meshheading:9888835-Matrix Metalloproteinase 9,
pubmed-meshheading:9888835-Metalloendopeptidases,
pubmed-meshheading:9888835-Models, Molecular,
pubmed-meshheading:9888835-Organophosphorus Compounds,
pubmed-meshheading:9888835-Protease Inhibitors,
pubmed-meshheading:9888835-Recombinant Proteins,
pubmed-meshheading:9888835-Stereoisomerism,
pubmed-meshheading:9888835-Structure-Activity Relationship
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
Design and synthesis of phosphinamide-based hydroxamic acids as inhibitors of matrix metalloproteinases.
|
|
pubmed:affiliation |
Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, Ohio 45040, USA.
|
|
pubmed:publicationType |
Journal Article
|
