Evidence map›Paper›PMID 39958438›Full record

ArticleWorld journal of gastroenterology2025

Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease

Han-Ning Xuan Yuan, Hyun Sung Kim, Gye Ryeol Park, Jae Eun Ryu, Ji Eun Kim, In Young Kang, Hye Young Kim, Seung Min Lee, Ju Hee Oh, Eileen L Yoon and 1 more

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Article in World journal of gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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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

11 authors.

Han-Ning Xuan YuanDepartment of Internal Medicine, Hanyang University School of Medicine, Seoul 04763, South Korea.
Hyun Sung KimDepartment of Pathology, Hanyang University School of Medicine, Seoul 04763, South Korea.
Gye Ryeol ParkDepartment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea.
Jae Eun RyuDepartment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea.
Ji Eun KimDepartment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea.
In Young KangDepartment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea.
Hye Young KimDepartment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea.
Seung Min LeeDepartment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea.
Ju Hee OhDepartment of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul 04763, South Korea.
Eileen L YoonDepartment of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul 01757, South Korea.
Dae Won JunDepartment of Internal Medicine, Hanyang University School of Medicine, Seoul 04763, South Korea. noshin@hanyang.ac.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMixed lineage kinase domain-like protein (MLKL) serves as a critical mediator in necroptosis, a form of regulated cell death linked to various liver diseases. This study aims to specifically investigate the role of MLKL's adenosine triphosphate (ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression. By focusing on this mechanism, we seek to identify potential therapeutic targets that can modulate MLKL activity, offering new strategies for the prevention and treatment of liver-related pathologies.

aimTo investigate the possibility of using the ATP-binding pocket-associated, necroptosis-independent MLKL pathway as a target for liver diseases.

methodsCell death following necroptosis stimuli was evaluated using cell proliferation assays, flow cytometry, and electron microscopy in various cells. The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation. Additionally, alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.

resultsWhile an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells, it did reduce the necroptosis-led expression of

conclusionMLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

Indexed as

Liver Diseases, AlcoholicNecroptosisProtein Kinase InhibitorsProtein KinasesAdenosine TriphosphateAnimalsDisease Models, AnimalHumansLiverMaleMiceMice, Inbred C57BLOrganoidsSignal TransductionAdenosine TriphosphateMLKL protein, humanMLKL protein, mouseProtein Kinase InhibitorsProtein KinasesAlcoholic liver diseaseCell deathMixed lineage kinase domain-like proteinMixed lineage kinase domain-like protein adenosine triphosphate binding inhibitorNecroptosisNon-alcoholic fatty liver diseaseRAW 264.7 cell

Identifiers

PMID39958438
PMCPMC11752702

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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.