TITLE : Application of Target - Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors
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Application of target-mediated drug disposition model to small molecule heat shock protein 90 inhibitors.
Replacement of hydrogen with fluorine within three pairs of structurally similar small molecule inhibitors of heat shock protein 90 (HSP90) resulted in differences in inhibition constants (K(i)) in vitro as well as marked differences in rat intravenous pharmacokinetic profiles. The difference in pharmacokinetic profiles between lower and higher affinity inhibitors (LAIs and HAIs, respectively) ...
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Replacement of hydrogenwith fluorine within three pairs of structurally similar small molecule inhibitors of heat shock protein 90 (HSP90) resulted in differences in inhibition constants (Ki) in vitro as well as marked differences in rat intravenous pharmacokinetic profiles. The difference in pharmacokinetic profiles between lower and higher affinity inhibitors (LAIs and HAIs, respectively) was...
متن کاملSmall Molecule Inhibitors to Disrupt Protein-protein Interactions of Heat Shock Protein 90 Chaperone Machinery
Heat shock protein 90 (Hsp90) is an adenosine triphosphate dependent molecular chaperone in eukaryotic cells that regulates the activation and maintenance of numerous regulatory and signaling proteins including epidermal growth factor receptor, human epidermal growth factor receptor 2, mesenchymal-epithelial transition factor, cyclin-dependent kinase-4, protein kinase B, hypoxia-inducible facto...
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Heat shock protein 90 (Hsp90) is an essential molecular chaperone in eukaryotes that facilitates the conformational maturation and function of a diverse protein clientele, including aberrant and/or over-expressed proteins that are involved in cancer growth and survival. A role for Hsp90 in supporting the protein homeostasis of cancer cells has buoyed interest in the utility of Hsp90 inhibitors ...
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The involvement of Hsp90 in progression of diseases like cancer, neurological disorders and several pathogen related conditions is well established. Hsp90, therefore, has emerged as an attractive drug target for many of these diseases. Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives, that display antitumor activity, have been developed and are under clinical trials....
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تاریخ انتشار 2013