کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10885686 1079897 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Can residence time offer a useful strategy to target agonist drugs for sustained GPCR responses?
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Can residence time offer a useful strategy to target agonist drugs for sustained GPCR responses?
چکیده انگلیسی
Residence time describes the how long a ligand is bound to its target, and is attracting interest in drug discovery as a potential means of improving clinical efficacy by increasing target coverage. This concept, as originally applied to antagonists, is more complicated for G-protein-coupled receptor (GPCR) agonists because of the transiency of receptor responses (via desensitization and internalization). However, in some cases sustained GPCR agonist responses have been observed, with evidence consistent with a role for slow binding kinetics. We propose a model to explain our understanding of how residence time and rebinding might influence sustained signaling by internalized receptors. We also highlight the anticipated benefit for drug discovery of fully understanding and exploiting these phenomena to target desirable receptor response profiles selectively.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Discovery Today - Volume 21, Issue 1, January 2016, Pages 90-96
نویسندگان
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