Evidence map›Paper›PMID 40341069›Full record

ArticleNature communications2025

Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro.

Haixia Su, Guofeng Chen, Hang Xie, Wanchen Li, Muya Xiong, Jian He, Hangchen Hu, Wenfeng Zhao, Qiang Shao, Minjun Li and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 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

12 authors.

Haixia Su *State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China. suhaixia1@simm.ac.cn.
Guofeng Chen *School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
Hang Xie *School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Wanchen Li *Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, 315100, China.
Muya XiongSchool of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.ORCID http://orcid.org/0000-0003-4639-5303
Jian HeState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China.
Hangchen HuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China.
Wenfeng ZhaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China.ORCID http://orcid.org/0000-0003-2517-4747
Qiang ShaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China.ORCID http://orcid.org/0000-0001-6460-3095
Minjun LiShanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201204, China.
Qiang ZhaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China. zhaoq@simm.ac.cn.ORCID http://orcid.org/0000-0001-6251-6676
Yechun XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, 201203, China. ycxu@simm.ac.cn.ORCID http://orcid.org/0000-0002-1581-6155

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The essential role of RIPK3 in necroptosis makes its inhibition a promising therapeutic strategy. However, the development of RIPK3 inhibitors has been hampered by on-target apoptosis and limited kinase selectivity. Inspired by the R69H mutation, which prevents on-target apoptosis by disrupting RIPK3 dimerization, we design LK-series inhibitors that effectively inhibit RIPK3 in biochemical assays and block TNF-α-induced necroptosis in both mouse L929 and human HT29 cells without inducing apoptosis. The representative compound, LK01003, shows high selectivity across a panel of 379 kinases. Our structural studies reveal that LK compounds act as Type I

Indexed as

Protein Kinase InhibitorsReceptor-Interacting Protein Serine-Threonine KinasesAnimalsApoptosisCell LineDrug DesignHT29 CellsHumansMiceNecroptosisStructure-Activity RelationshipTumor Necrosis Factor-alphaProtein Kinase InhibitorsReceptor-Interacting Protein Serine-Threonine KinasesRIPK3 protein, humanRipk3 protein, mouseTumor Necrosis Factor-alpha

Identifiers

PMID40341069
PMCPMC12062462

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.