Bioorthogonal Bond Cleavage Chemistry for On-demand Prodrug Activation: Opportunities and Challenges

Time- and space-resolved drug delivery is highly demanded for cancer treatment, which, however, can barely be achieved with a traditional prodrug strategy. In recent years, the prodrug strategy based on a bioorthogonal bond cleavage chemistry has emerged with the advantages of high temporospatial re...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2023-12, Vol.66 (24), p.16546-16567
Main Authors: Min, Qingqiang, Ji, Xingyue
Format: Article
Language:English
Subjects:
Drug Delivery Systems
Prodrugs - chemistry
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Summary:Time- and space-resolved drug delivery is highly demanded for cancer treatment, which, however, can barely be achieved with a traditional prodrug strategy. In recent years, the prodrug strategy based on a bioorthogonal bond cleavage chemistry has emerged with the advantages of high temporospatial resolution over drug activation and homogeneous activation irrespective of individual heterogeneity. In the past five years, tremendous progress has been witnessed in this field with one such bioorthogonal prodrug entering Phase II clinical trials. This Perspective aims to highlight these new advances (2019–2023) and critically discuss their pros and cons. In addition, the remaining challenges and potential strategic directions for future progress will also be included.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.3c01459