Evidence map›Paper›PMID 38355723›Full record

ArticleNature chemical biology2024

Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.

Xiaoyu Zhou, Cheng Zhao, Haiyan Xu, Yixiang Xu, Li Zhan, Pei Wang, Jingyi He, Taotao Lu, Yueling Gu, Yan Yang and 13 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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

24 citing papers in PubMed, 30 citations in OpenAlex.

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  12. Activation of Kir4.1 Channels by 2-D08 Promotes Myelin Repair in Multiple Sclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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  14. Genetic contributions to brain criticality and its relationship with human cognitive functions.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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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

23 authors at 6 institutions in 1 country.

Xiaoyu Zhou *State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Cheng Zhao *Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Haiyan Xu *State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yixiang XuState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.ORCID http://orcid.org/0000-0003-4128-8832
Li ZhanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Pei WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Jingyi HeState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Taotao LuState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
Yueling GuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yan YangLiangzhu Laboratory, Zhejiang University School of Medicine, New Cornerstone Science Laboratory, Zhejiang University, Hangzhou, China.
Chanjuan XuCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0002-5640-1896
Yiyang ChenCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Yuxuan LiuCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Yue ZengState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Fuyun TianZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, China.
Qian ChenDepartment of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xin XieState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0003-2314-4800
Jianfeng LiuCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0002-0284-8377
Hailan HuLiangzhu Laboratory, Zhejiang University School of Medicine, New Cornerstone Science Laboratory, Zhejiang University, Hangzhou, China.
Jian LiState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.ORCID http://orcid.org/0000-0002-7521-8798
Yueming ZhengState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. zhengyueming@simm.ac.cn.ORCID http://orcid.org/0000-0003-0677-0316
Jiangtao GuoDepartment of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. jiangtaoguo@zju.edu.cn.ORCID http://orcid.org/0000-0002-8850-286X
Zhaobing GaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. zbgao@simm.ac.cn.ORCID http://orcid.org/0000-0001-8931-5508
Chinese Academy of Sciences · CNZhejiang University · CNHuazhong University of Science and Technology · CNEast China University of Science and Technology · CNNanjing University of Chinese Medicine · CNHenan University · CN

Funding

China National Funds for Distinguished Young Scientists 81825021National Natural Science Foundation of China (National Science Foundation of China) 2021ZD0200900National Natural Science Foundation of China (National Science Foundation of China) 92169202Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 2018SHZDZX05Youth Innovation Promotion Association of the Chinese Academy of Sciences (Youth Innovation Promotion Association CAS) 2020284
6 · The paper itself

Abstract

Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depression. Here, we discovered a series of Kir4.1 inhibitors through high-throughput screening. Lys05, the most potent one thus far, effectively suppressed native Kir4.1 channels while displaying high selectivity against established targets for rapid-onset antidepressants. Cryogenic-electron microscopy structures combined with electrophysiological characterizations revealed Lys05 directly binds in the central cavity of Kir4.1. Notably, a single dose of Lys05 reversed the Kir4.1-driven depression-like phenotype and exerted rapid-onset (as early as 1 hour) antidepressant actions in multiple canonical depression rodent models with efficacy comparable to that of (S)-ketamine. Overall, we provided a proof of concept that Kir4.1 is a promising target for rapid-onset antidepressant effects.

Indexed as

Antidepressive AgentsPotassium Channels, Inwardly RectifyingAnimalsDepressionDisease Models, AnimalHumansKcnj10 ChannelMajor Depressive DisorderMaleMiceMice, Inbred C57BLPotassium Channel BlockersRatsAntidepressive AgentsKcnj10 ChannelPotassium Channel BlockersPotassium Channels, Inwardly Rectifying

Identifiers

PMID38355723
OpenAlexW4391822219

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.