ArticleNucleic acids research2015
Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 68 citations in OpenAlex.
- Expedient single-round selection of hyper-modified aptamer targeting insulin receptor from over-represented dually nucleobase-modified DNA libraries.Nature communications · 2026Article
- Navigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics.Chemical science · 2026Review
- CD25-Targeted Aptamer-Drug Conjugate for the Treatment of CD25-Expressing Hematological Malignancies.Pharmaceutics · 2026Article
- Aptamers in Drug Delivery Development.Materials today (Kidlington, England) · 2025Article
- Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.Experimental & molecular medicine · 2025Article
- Allosteric targeted drug delivery for enhanced blood-brain barrier penetration via mimicking transmembrane domain interactions.Nature communications · 2025Article
- Analysis of cell signaling profiles induced by DNA aptamer-based FGFR1 agonist.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024Article
- A stepwise activation model for the insulin receptor.Experimental & molecular medicine · 2023Review
- Aptamer-Based Probes for Cancer Diagnostics and Treatment.Life (Basel, Switzerland) · 2022Review
- Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures.Nature communications · 2022Article
- The Insulin Receptor: An Important Target for the Development of Novel Medicines and Pesticides.International journal of molecular sciences · 2022Review
- Membrane Hormone Receptors and Their Signaling Pathways as Targets for Endocrine Disruptors.Journal of xenobiotics · 2022Review
- Minimizing Mitogenic Potency of Insulin Analogues Through Modification of a Disulfide Bond.Frontiers in endocrinology · 2022Article
- Recent Progress and Opportunities for Nucleic Acid Aptamers.Life (Basel, Switzerland) · 2021Review
- A hotspot for enhancing insulin receptor activation revealed by a conformation-specific allosteric aptamer.Nucleic acids research · 2021Article
- Enlarging the Toolbox Against Antimicrobial Resistance: Aptamers and CRISPR-Cas.Frontiers in microbiology · 2021Review
- Targeted Therapy of Hepatocellular Carcinoma Using Gemcitabine-Incorporated GPC3 Aptamer.Pharmaceutics · 2020Article
- Non-Invasive Delivery of Therapeutics into the Brain: The Potential of Aptamers for Targeted Delivery.Biomedicines · 2020Review
- A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application.Science advances · 2020Article
- Lipid mediators of insulin signaling in diabetic kidney disease.American journal of physiology. Renal physiology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability to activate protein function through aptamer-protein interaction has not been well-elucidated. To investigate their potential as target-specific agonists, we used SELEX to generate aptamers to the insulin receptor (IR) and identified an agonistic aptamer named IR-A48 that specifically binds to IR, but not to IGF-1 receptor. Despite its capacity to stimulate IR autophosphorylation, similar to insulin, we found that IR-A48 not only binds to an allosteric site distinct from the insulin binding site, but also preferentially induces Y1150 phosphorylation in the IR kinase domain. Moreover, Y1150-biased phosphorylation induced by IR-A48 selectively activates specific signaling pathways downstream of IR. In contrast to insulin-mediated activation of IR, IR-A48 binding has little effect on the MAPK pathway and proliferation of cancer cells. Instead, AKT S473 phosphorylation is highly stimulated by IR-A48, resulting in increased glucose uptake both in vitro and in vivo. Here, we present IR-A48 as a biased agonist able to selectively induce the metabolic activity of IR through allosteric binding. Furthermore, our study also suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.