Evidence map›Paper›PMID 41980950›Full record

ArticleNature communications2026

Rational design of a Kappa opioid receptor peptide agonist with attenuated β-arrestin signaling.

Huanhuan Zhang, Ruolan Wang, Pan Shi, Gaoming Wang, Qingjun Zhu, Xinheng He, Youwei Xu, Qingning Yuan, Wen Hu, Kai Wu and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Huanhuan Zhang *Department of Endocrinology, the First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, P. R. China.
Ruolan Wang *The State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0009-1538-3503
Pan Shi *Department of Endocrinology, the First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, P. R. China. shipan@ustc.edu.cn.
Gaoming Wang *Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qingjun Zhu *High Magnetic Field Laboratory, Hefei Institute of Physical Science, Chinese Academy of Sciences, Anhui, China.
Xinheng HeThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0001-7813-5480
Youwei XuThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0001-8069-7511
Qingning YuanThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Wen HuThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Kai WuThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yong ZhengAnhui Engineering Laboratory of Peptide Drug, University of Science and Technology of China, Anhui, China.
Li ZhouAnhui Engineering Laboratory of Peptide Drug, University of Science and Technology of China, Anhui, China.
Jun LiangDepartment of Endocrinology, the First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, P. R. China.
Pei LvSchool of Biomedical Engineering, Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, Jiangsu, China.
Ziyan XuDepartment of Endocrinology, the First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, P. R. China.
Fan YangDepartment of Endocrinology, the First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, P. R. China.
Yingbin LiuDepartment of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0001-6110-0185
Youwen ZhuangDepartment of Pharmaceutical and Artificial-Intelligence Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.ORCID http://orcid.org/0000-0002-1380-8047
H Eric XuThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. eric.xu@simm.ac.cn.ORCID http://orcid.org/0000-0002-6829-8144
Yue WangThe State Key Laboratory of Drug Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. wangyue1@simm.ac.cn.ORCID http://orcid.org/0000-0002-3716-2922
Changlin TianDepartment of Endocrinology, the First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, P. R. China. cltian@ustc.edu.cn.ORCID http://orcid.org/0000-0001-9315-900X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 22437005
6 · The paper itself

Abstract

Difelikefalin is an FDA-approved κ-opioid receptor (KOR) peptide agonist used to treat chronic pruritus. However, as a balanced agonist that activates both G protein and β-arrestin pathways, difelikefalin remains associated with undesirable side effects linked to β-arrestin signaling. Here, we report the cryo-EM structure of the difelikefalin-KOR-Gi complex, identifying Y320

Indexed as

beta-ArrestinsReceptors, Opioid, kappaAnimalsCryoelectron MicroscopyDrug DesignHEK293 CellsHumansMiceMolecular Dynamics SimulationProtein BindingPruritusSignal Transductionbeta-ArrestinsReceptors, Opioid, kappa

Identifiers

PMID41980950
PMCPMC13279772

What OpenQuestion holds

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Registered trials

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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.