Center for System Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Center for System Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
Adv Drug Deliv Rev. 2019 Nov-Dec;151-152:262-288. doi: 10.1016/j.addr.2018.01.019. Epub 2018 Feb 2.
Non-invasive measurement of drug-target engagement can provide critical insights in the molecular pharmacology of small molecule drugs. Fluorescence polarization/fluorescence anisotropy measurements are commonly employed in protein/cell screening assays. However, the expansion of such measurements to the in vivo setting has proven difficult until recently. With the advent of high-resolution fluorescence anisotropy microscopy it is now possible to perform kinetic measurements of intracellular drug distribution and target engagement in commonly used mouse models. In this review we discuss the background, current advances and future perspectives in intravital fluorescence anisotropy measurements to derive pharmacokinetic and pharmacodynamic measurements in single cells and whole organs.
非侵入性的药物靶点结合测量可以为小分子药物的分子药理学提供关键的见解。荧光偏振/荧光各向异性测量通常用于蛋白质/细胞筛选测定。然而，直到最近，这种测量方法才被扩展到体内环境。随着高分辨率荧光各向异性显微镜的出现，现在可以在常用的小鼠模型中进行细胞内药物分布和靶标结合的动力学测量。在这篇综述中，我们讨论了活体荧光各向异性测量的背景、当前进展和未来展望，以从单个细胞和整个器官中获得药代动力学和药效动力学测量。
