ArticleNature chemistry2025
Tumour-specific STING agonist synthesis via a two-component prodrug system.
Article in Nature chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Driving tumor-associated macrophages to a CXCL9Cell reports. Medicine · 2026Article
- Roles of the cGAS-STING signaling pathway in viral latency.Journal of virology · 2026Review
- Antitumor effects of STING agonists on nervous system tumors via tumor-intrinsic STING-STAT1-mediated HMGN2 expression.Cancer biology & medicine · 2026Article
- Glucan-Based Nanoparticles Empower Precision Cancer Immunotherapy: Design Strategies, Immune Reprogramming Mechanisms, and Clinical Translation Prospects.International journal of nanomedicine · 2026Review
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Authors and funding
14 authors.
Funding
Abstract
Pharmacological activation of STING holds promise in cancer treatment. A recent trend is the development of tumour-specific or conditionally activated STING agonists for enhanced safety and efficacy. Here we explore an unconventional prodrug activation strategy for on-tumour synthesis of a potent agonist. Leveraging the unique mechanism of MSA2, a small-molecule agonist that dimerizes non-covalently before binding to STING, we showed that its analogues bearing reactive functional groups readily and selectively form covalent dimers under mild conditions and in complex environments. We identified a reacting pair that led to a thioether-linked dimer with submicromolar potency in cell-based assays. Caging one of the reactants with a self-immolative β-glucuronide moiety resulted in a two-component prodrug system that near-exclusively formed the active compounds in tumours overexpressing β-glucuronidase. These results exemplify the use of small-molecule recognition for on-site generation of active compounds from benign precursors.
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Registered trials
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