Structural biology contributions to tyrosine kinase drug discovery

Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provi...

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Veröffentlicht in:Current opinion in cell biology 2009-04, Vol.21 (2), p.280-287
Hauptverfasser: Cowan-Jacob, Sandra W, Möbitz, Henrik, Fabbro, Doriano
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container_end_page 287
container_issue 2
container_start_page 280
container_title Current opinion in cell biology
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creator Cowan-Jacob, Sandra W
Möbitz, Henrik
Fabbro, Doriano
description Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provided a rational basis for obtaining selective inhibitors. Important progress has been made recently, both in academia and in the pharmaceutical industry, with respect to solving structures of inactive, multidomain or protein–protein complexes of kinases, which helps our understanding of the dynamics of regulation of kinase activity. This leads to a better understanding of how mutations lead to activation of kinases and resistance, in addition to providing opportunities for novel modes of targeting kinases.
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subjects Binding Sites
Drug Design
Drug Discovery
Humans
Internal Medicine
Molecular Structure
Mutation
Neoplasms - drug therapy
Protein Conformation
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - therapeutic use
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - chemistry
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Structure-Activity Relationship
Substrate Specificity
title Structural biology contributions to tyrosine kinase drug discovery
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