Abstract
A strategy of full-site occupancy and stereospecific recognition in the triphosphate subsite was used to specifically inhibit two protein kinases HER-2 and HER-4 from the EGFR family. The SAR profiles of a panel of adenosine-anchored bicyclic heterocycles against HER-2 and HER-4 indicated that specificity can be derived for highly homologous protein kinases from stereospecific recognition in the triphosphate-subsite.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine / chemistry*
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Benzamides
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Enzyme Inhibitors / chemistry
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / chemistry*
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ErbB Receptors / metabolism
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Imatinib Mesylate
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Models, Molecular
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Molecular Probes*
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Phosphates / chemistry*
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Piperazines / chemistry
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Pyrimidines / chemistry
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Receptor, ErbB-2 / antagonists & inhibitors
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Receptor, ErbB-2 / chemistry*
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Receptor, ErbB-2 / metabolism
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Receptor, ErbB-4
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Structure-Activity Relationship
Substances
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Benzamides
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Enzyme Inhibitors
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Molecular Probes
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Phosphates
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Piperazines
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Pyrimidines
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Imatinib Mesylate
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ErbB Receptors
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Receptor, ErbB-2
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Receptor, ErbB-4
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Adenosine