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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5314
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pubmed:dateCreated |
1997-5-23
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pubmed:databankReference |
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pubmed:abstractText |
A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fgfr1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Fibroblast Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fibroblast Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
955-60
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9139660-3T3 Cells,
pubmed-meshheading:9139660-Adenosine Triphosphate,
pubmed-meshheading:9139660-Amino Acid Sequence,
pubmed-meshheading:9139660-Animals,
pubmed-meshheading:9139660-Crystallography, X-Ray,
pubmed-meshheading:9139660-Enzyme Inhibitors,
pubmed-meshheading:9139660-Hydrogen Bonding,
pubmed-meshheading:9139660-Mice,
pubmed-meshheading:9139660-Models, Molecular,
pubmed-meshheading:9139660-Phosphorylation,
pubmed-meshheading:9139660-Phosphotyrosine,
pubmed-meshheading:9139660-Piperazines,
pubmed-meshheading:9139660-Protein-Tyrosine Kinases,
pubmed-meshheading:9139660-Pyrroles,
pubmed-meshheading:9139660-Receptor, Epidermal Growth Factor,
pubmed-meshheading:9139660-Receptor, Fibroblast Growth Factor, Type 1,
pubmed-meshheading:9139660-Receptor, Insulin,
pubmed-meshheading:9139660-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:9139660-Receptors, Fibroblast Growth Factor,
pubmed-meshheading:9139660-Receptors, Platelet-Derived Growth Factor
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pubmed:year |
1997
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pubmed:articleTitle |
Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.
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pubmed:affiliation |
Department of Pharmacology, New York University Medical Center, New York, NY 10016, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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