Department of Urology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Urology Minimally Invasive Engineering Center, Shenzhen 518020, Guangdong, China; Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore.
Department of Urology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Urology Minimally Invasive Engineering Center, Shenzhen 518020, Guangdong, China; Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.
Pharmacol Ther. 2020 Dec;216:107690. doi: 10.1016/j.pharmthera.2020.107690. Epub 2020 Sep 25.
Natural products (NPs) have been an important source of therapeutic drugs in clinic use and contributed many chemical probes for research. The usefulness of NPs is however often marred by the incomplete understanding of their direct cellular targets. A number of experimental methods for drug target identification have been developed over the years. One class of methods, termed "label-free" methodology, exploits the energetic and biophysical features accompanying the association of macromolecules with drugs and other compounds in their native forms. Herein we review the working principles, assay implementations, and key applications of the most important approaches, and also give examples where they have been applied to NPs. We also assess the key advantages and limitations of each method. Furthermore, we address when and how the label-free methodology can be particularly useful considering some of the unique features of NP chemistry and bioactivation.
天然产物（NPs）一直是临床应用中治疗药物的重要来源，并为研究提供了许多化学探针。然而，NPs 的有用性常常因对其直接细胞靶标的不完全了解而受到影响。多年来已经开发了许多用于药物靶标识别的实验方法。一类方法，称为“无标记”方法，利用与药物结合的大分子以及它们在天然形式下与其他化合物结合时伴随的能量和生物物理特征。本文综述了最重要方法的工作原理、测定实施以及关键应用，并举例说明了它们在 NPs 中的应用。我们还评估了每种方法的主要优点和局限性。此外，我们还考虑了 NP 化学和生物活化的一些独特特征，讨论了在何时以及如何使用无标记方法会特别有用。
