Translating slow-binding inhibition kinetics into cellular and in vivo effects

Many drug candidates fail in clinical trials due to a lack of efficacy from limited target engagement or an insufficient therapeutic index. Minimizing off-target effects while retaining the desired pharmacodynamic (PD) response can be achieved by reduced exposure for drugs that display kinetic selec...

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Veröffentlicht in:Nat Chem Biol
Hauptverfasser: Walkup, Grant K., You, Zhiping, Ross, Philip L., Allen, Eleanor K. H., Daryaee, Fereidoon, Hale, Michael R., O’Donnell, John, Ehmann, David E., Schuck, Virna J. A., Buurman, Ed T., Choy, Allison L., Hajec, Laurel, Murphy-Benenato, Kerry, Marone, Valerie, Patey, Sara A., Grosser, Lena A., Johnstone, Michele, Walker, Stephen G., Tonge, Peter J., Fisher, Stewart L.
Format: Artigo
Sprache:Inglês
Veröffentlicht: 2015
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Article
Online Zugang:https://ncbi.nlm.nih.gov/pmc/articles/PMC4536915/
https://ncbi.nlm.nih.gov/pubmed/25894085
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1038/nchembio.1796
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