Evidence map›Paper›PMID 39379684›Full record

ArticleActa pharmacologica Sinica2025

LN-439A, a novel BAP1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5.

Tian-Tian Wang, Long-Long Zhang, Fu-Bing Li, Jie Zhang, Zhi-Bi Zhang, Da-Zhao Mi, Jian Sun, Hong-Yan Zhang, Chun-Yan Wang, Yi-Hua Chen and 1 more

Abstract read
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In one paragraph

Article in Acta pharmacologica Sinica, 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

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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  4. Review
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.

Tian-Tian Wang *School of Life Science, University of Science and Technology of China, Hefei, 230027, China.
Long-Long Zhang *Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China.
Fu-Bing Li *Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China.
Jie ZhangShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Zhi-Bi ZhangAcademy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China.
Da-Zhao MiShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Jian SunThe Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China.
Hong-Yan ZhangKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China.
Chun-Yan WangDepartment of the Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China. chunyan740729@sina.com.
Yi-Hua ChenShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. chenyihua@kmmu.edu.cn.
Ce-Shi ChenKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China. chenc@kmmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1‒KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-β-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1‒KLF5 axis.

Indexed as

Antineoplastic AgentsApoptosisBreast NeoplasmsCell ProliferationKruppel-Like Transcription FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseAnimalsCell Line, TumorCell MovementFemaleHumansMiceMice, Inbred BALB CMice, NudeStructure-Activity RelationshipAntineoplastic AgentsBAP1 protein, humanKLF5 protein, humanKruppel-Like Transcription FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseBAP1BLBCdeubiquitinationKLF5LN-439A

Identifiers

PMID39379684
PMCPMC11845570

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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.