Evidence map›Paper›PMID 41054857›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

TSHR-Targeting Nucleic Acid Aptamer Treats Graves' Ophthalmopathy via Novel Allosteric Inhibition.

Yanchen Zhang, Ende Wu, Weibin Liu, Ling Zeng, Neng Ling, Hongmei Wang, Zhixing Li, Shuang Yao, Tonghe Pan, Xuanwen Li and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Yanchen ZhangState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Ende WuState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Weibin LiuState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Ling ZengState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Neng LingState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Hongmei WangState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Zhixing LiState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Shuang YaoState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Tonghe PanState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Xuanwen LiState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Yate HuangState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Xiaojing LiState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Yunhai TuState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Wentao YanState Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Jianzhang WuOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325000, China.
Mao YeMolecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, Hunan Research Center of the Basic Discipline for Cell Signaling, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China.
Wencan WuOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, 325000, China.ORCID https://orcid.org/0000-0001-8556-1197

Funding

Key science and technology program of Wenzhou ZY2022021Ministry and the province of Zhejiang Medical and Health Science and Technology Project WKJ-ZJ-2336National Key R&D Program of China 2021YFA0909400National Key R&D Program of China 2021YFA1101200the National Natural Science Foundation of China 22334005the National Natural Science Foundation of China 32350026the National Natural Science Foundation of China 82171048the National Natural Science Foundation of China 92253201
6 · The paper itself

Abstract

Graves' ophthalmopathy (GO) is an autoimmune disorder marked by orbital inflammation and tissue remodeling, leading to irreversible disfigurement and vision loss. The current first-line glucocorticoid therapy remains palliative, underscoring the critical need for mechanism-based interventions. Autoantibodies against thyrotropin receptor (TSHR) in GO patients highlight its therapeutic potential, yet TSHR inhibitor development faces challenges, including low potency, off-target effects, and mechanistic constraints. To overcome this therapeutic void, YC3, a TSHR-targeting nucleic acid aptamer, has been developed through an innovative approach that combines protein-targeting cell-SELEX with functional selection. YC3 exhibits nanomolar affinity alongside robust pharmacodynamic efficacy. In vitro, YC3 significantly reverses thyroid-stimulating antibodies (TSAbs)-driven hyperactivation in primary human orbital fibroblasts, thereby suppressing pathogenic hallmarks of fibroblasts. In vivo, therapeutic administration of YC3 significantly alleviates ocular symptoms in a GO mouse model. Mechanistic investigations reveal that YC3 binds to a previously unidentified allosteric site within the leucine-rich repeat domain of TSHR, consequently inhibiting receptor activation. Collectively, this study not only identifies YC3 as a promising TSHR-targeting therapeutic candidate but also unveils a novel allosteric site for next-generation inhibitors. These findings highlight the potential of aptamers in both dissecting receptor mechanisms and uncovering cryptic druggable sites, thereby bridging structural biology with targeted drug development.

Indexed as

Aptamers, NucleotideGraves OphthalmopathyReceptors, ThyrotropinAllosteric RegulationAnimalsDisease Models, AnimalFibroblastsHumansMiceAptamers, NucleotideReceptors, Thyrotropinallosteric inhibitionGraves' ophthalmopathynucleic acid aptamertargeted therapythyrotropin receptor

Identifiers

PMID41054857
PMCPMC12822413

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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.