Pan Sijun, Ding Aixiang, Li Yisi, Sun Yaxin, Zhan Yueqin, Ye Zhenkun, Song Ning, Peng Bo, Li Lin, Huang Wei, Shao Huilin
The Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen 361005, China.
Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.
Chem Soc Rev. 2023 Aug 14;52(16):5706-5743. doi: 10.1039/d3cs00056g.
Over the past decade, remarkable advances have been witnessed in the development of small-molecule probes. These molecular tools have been widely applied for interrogating proteins, pathways and drug-target interactions in preclinical research. While novel structures and designs are commonly explored in probe development, the clinical translation of small-molecule probes remains limited, primarily due to safety and regulatory considerations. Recent synergistic developments - interfacing novel chemical probes with complementary analytical technologies - have introduced and expedited diverse biomedical opportunities to molecularly characterize targeted drug interactions directly in the human body or through accessible clinical specimens (, blood and ascites fluid). These integrated developments thus offer unprecedented opportunities for drug development, disease diagnostics and treatment monitoring. In this review, we discuss recent advances in the structure and design of small-molecule probes with novel functionalities and the integrated development with imaging, proteomics and other emerging technologies. We further highlight recent applications of integrated small-molecule technologies for the molecular analysis of drug-target interactions, including translational applications and emerging opportunities for whole-body imaging, tissue-based measurement and blood-based analysis.
在过去十年中，小分子探针的发展取得了显著进展。这些分子工具已广泛应用于临床前研究中对蛋白质、信号通路和药物-靶点相互作用的研究。虽然在探针开发中通常会探索新的结构和设计，但小分子探针的临床转化仍然有限，主要是出于安全性和监管方面的考虑。最近的协同发展——将新型化学探针与互补分析技术相结合——已经引入并加速了各种生物医学机会，能够直接在人体中或通过可获取的临床标本（如血液和腹水）对靶向药物相互作用进行分子表征。因此，这些综合发展为药物开发、疾病诊断和治疗监测提供了前所未有的机会。在本综述中，我们讨论了具有新功能的小分子探针在结构和设计方面的最新进展，以及与成像、蛋白质组学和其他新兴技术的综合发展。我们还进一步强调了集成小分子技术在药物-靶点相互作用分子分析中的最新应用，包括转化应用以及全身成像、基于组织的测量和基于血液的分析等新兴机会。
