Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2003-10-16
pubmed:abstractText
It has been reported that the diaryl urea class of p38alpha inhibitors binds to p38 map kinase with both high affinity and slow binding kinetics (Pargellis et al. Nat. Struct. Biol. 2002, 9, 268-272). The slow binding kinetics of this class of inhibitors is believed to be the result of binding to an allosteric pocket adjacent to the p38alpha active site. The use of traditional kinetic and equilibrium methods to measure the binding affinity of this class of compounds has created many challenges for determination of structure-activity relationships (SAR). The thermal denaturation method provides a means of measuring high-affinity interactions. In this paper, the method of thermal denaturation will be described as it has been applied to the diaryl urea class of p38 map kinase inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4669-75
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14561086-Algorithms, pubmed-meshheading:14561086-Allosteric Site, pubmed-meshheading:14561086-Animals, pubmed-meshheading:14561086-Binding Sites, pubmed-meshheading:14561086-Calorimetry, Differential Scanning, pubmed-meshheading:14561086-Enzyme Inhibitors, pubmed-meshheading:14561086-Fluorescence, pubmed-meshheading:14561086-Heating, pubmed-meshheading:14561086-Humans, pubmed-meshheading:14561086-Mice, pubmed-meshheading:14561086-Mitogen-Activated Protein Kinase 14, pubmed-meshheading:14561086-Mitogen-Activated Protein Kinases, pubmed-meshheading:14561086-Protein Binding, pubmed-meshheading:14561086-Protein Denaturation, pubmed-meshheading:14561086-Protein Folding, pubmed-meshheading:14561086-Spectrophotometry, Ultraviolet, pubmed-meshheading:14561086-Structure-Activity Relationship, pubmed-meshheading:14561086-Thermodynamics, pubmed-meshheading:14561086-Urea
pubmed:year
2003
pubmed:articleTitle
Thermal denaturation: a method to rank slow binding, high-affinity P38alpha MAP kinase inhibitors.
pubmed:affiliation
Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P. O. Box 368, Ridgefield, Connecticut 06877, USA. rkroe@rdg.boehringer-ingelheim.com
pubmed:publicationType
Journal Article