Ahn Sung, Sanchez-Langeling Benjamin, Lee Jeong Heon, Henary Maged, Bao Kai, Choi Hak Soo
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Boston, MA 02129, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 01238, USA.
Adv Photonics Res. 2023 Aug;4(8). doi: 10.1002/adpr.202300036. Epub 2023 Jun 2.
Hepatobiliary and renal excretions are the two major in vivo elimination pathways, of which prediction is particularly important for the optimization of systemic and/or target-site exposure of new near-infrared (NIR) fluorescent contrast agents. To characterize the physicochemical descriptors associated with each clearance route, a compound library containing more than 760 NIR fluorophores is analyzed and systematically reviewed in this study. Although there are a host of biochemical and physiological mechanisms that ultimately determine the in vivo fate of any given molecule, the physicochemical properties of contrast agents including molecular weight, hydrophobicity, topological polar surface area, molecular charges, and hydrogen/rotatable bonds are often indicative of each clearance route. The approach developed is anticipated to be useful in early lead identification studies when selecting NIR fluorescent contrast agents from large database screenings. It may also be applied to prioritize synthetically feasible chemical modifications during lead compound optimization.
肝胆和肾脏排泄是体内两种主要的消除途径，对于优化新型近红外（NIR）荧光造影剂的全身和/或靶部位暴露而言，预测这两种途径尤为重要。为了表征与每种清除途径相关的物理化学描述符，本研究分析并系统回顾了一个包含760多种近红外荧光团的化合物库。尽管有许多生化和生理机制最终决定任何给定分子的体内命运，但造影剂的物理化学性质，包括分子量、疏水性、拓扑极性表面积、分子电荷以及氢键/可旋转键，往往能指示每种清除途径。预计所开发的方法在从大型数据库筛选中选择近红外荧光造影剂的早期先导化合物鉴定研究中会很有用。它也可用于在先导化合物优化过程中对合成上可行的化学修饰进行优先级排序。
