Evidence map›Paper›PMID 39832720›Full record

ArticleJournal of advanced research2025

A novel small molecule NJH-13 induces pyroptosis via the Ca

Xianxiang Dong, Jiahui Nie, Aiying Huang, Li Chen, Erkang Zang, Zhengrui Xiang, Xiaojiang Hao, Shengjiao Yan, Xiao Ding, Yuhan Zhao

Abstract read
In one paragraph

Article in Journal of advanced research, 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

10 authors.

Xianxiang DongState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Jiahui NieSchool of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
Aiying HuangState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
Li ChenSchool of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
Erkang ZangState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; School of Life Sciences, Yunnan University, Kunming 650091, PR China.
Zhengrui XiangState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Xiaojiang HaoState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing 100730, PR China.
Shengjiao YanSchool of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: yansj@ynu.edu.cn.
Xiao DingState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing 100730, PR China. Electronic address: dingxiao@mail.kib.ac.cn.
Yuhan ZhaoState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China. Electronic address: zhaoyuhan@mail.kib.ac.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPyroptosis represents a mode of programmed necrotic cell death (PCD), mediated by members of gasdermin family (GSDMs), such as GSDME. It is emerging as a promising approach for combating cancer. Notably, GSDME is the key modulator for the switch between apoptosis and pyroptosis in cells. However, GSDME is often downregulated in many malignancies, including lung adenocarcinoma.

objectiveTo identify novel pyroptosis inducers in non-small cell lung cancer (NSCLC) and dissect the underlying mechanism.

methodsPyroptosis was examined by live cell imaging, PI/Hoechst/Annexin V staining, LDH release assay, ELISA, and western blot assays. DARTS, CETSA, molecular docking was used to identify the target of NJH-13. RNA-seq, qPCR, chromatin immunoprecipitation (ChIP), dual luciferase assays were used elucidate the mechanism.

resultsIn this study, NJH-13, an N-containing heterocycle, was screened out and identified to possess the ability to activate GSDME, consequently triggering pyroptosis in NSCLC cells. By using the DARTS strategy, transient receptor potential cation channel subfamily V member 5 (TRPV5) was identified as a potential target of NJH-13. NJH-13 increased intracellular calcium level and triggered oxidative stress, both of which are critical events leading to pyroptosis mediated by GSDME. Mechanistically, NJH-13 enhanced the transcription of GSDME via the protein kinase B (AKT)/forkhead box transcription factor O1 (FOXO1) signaling pathway. ChIP revealed that FOXO1 bound directly to the promoter region of GSDME, thus triggering the GSDME-mediated pyroptosis. Pharmacological and genetic activation of AKT or inhibition of FOXO1 partially rescued NJH-13-induced pyroptotic cell death. Moreover, NJH-13 treatment suppressed tumor growth in vivo.

conclusionTaken together, our results revealed that TRPV5 is a distinctive target for manipulating pyroptosis and provided evidence that NJH-13 functions as a potential anti-cancer agent capable of triggering pyroptosis in NSCLC cells.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsPyroptosisTRPV Cation ChannelsAnimalsCalciumCell Line, TumorForkhead Box Protein O1GasderminsHumansMicePhosphate-Binding ProteinsProto-Oncogene Proteins c-aktSignal TransductionCalciumForkhead Box Protein O1FOXO1 protein, humanGasderminsGSDME protein, humanPhosphate-Binding ProteinsProto-Oncogene Proteins c-aktTRPV Cation ChannelsFOXO1GSDMENSCLCOxidative stressPyroptosisTRPV5

Identifiers

PMID39832720
PMCPMC12627346

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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.