Evidence map›Paper›PMID 42663780›Full record

ArticleNatural products and bioprospecting2026

β-carboline derivative Z86 alleviates pulmonary fibrosis via suppressing TGF-β/Smad signaling.

Yuyang Wang, Shaohua Zhang, Rong Geng, Ruiying Wang, Ying Huang, Gang Xu, Lingmei Kong, Yan Li

Abstract read
In one paragraph

Article in Natural products and bioprospecting, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Yuyang WangKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China.
Shaohua ZhangKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China.
Rong GengKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China.
Ruiying WangKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China.
Ying HuangKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China.
Gang XuKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China.
Lingmei KongKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China. konglingmei@ynu.edu.cn.
Yan LiKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of EducationYunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P.R. China. yan.li@ynu.edu.cn.

Funding

Applied Basic Research Foundation of Yunnan Province 202301AS070022National Natural Science Foundation of China 32260159National Natural Science Foundation of China 82360725
6 · The paper itself

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant fibroblast proliferation and excessive expression and deposition of extracellular matrix (ECM) by myofibroblasts, ultimately resulting in progressive and irreversible disorder or even loss of the pulmonary function. IPF is incurable with limited therapeutic options and low survival rate, thus the discovery of the therapeutic potential agents for IPF is in urgent need. Here, we identified isopropyl 9-ethyl-1-(naphthalen-1-yl)-9H-pyrido[3,4-b] indole-3-carboxylate (Z86) as a promising bioactive agent against Bleomycin (BLM) induced pulmonary fibrotic mice with the lung abnormalities including histological alteration, accumulation of ECM, as well as markers of EMT (epithelial-mesenchymal transition) were all relieved upon Z86 treatment in C57BL/6 mice. Consistent to the activity in vivo, Z86 decreased TGF-β induced cell migration, fibrotic marker expression, and myofibroblast activation in A549 and HFL1 cells. In further mechanism of action study of Z86 against IPF, we found TGF-β (transforming growth factor β) /Smad2/3 signaling pathway was substantially attenuated in TGF-β treated A549 and HFL1 cells, with remarkably decreased protein level of Smad2/3. Further, we identified Z86 as a novel USP15 inhibitor. Correspondingly, Z86 interacted with USP15, promoted the ubiquitination and degradation of Smad2/3 and disrupted TGF-β/Smad2/3 signaling pathway. Taken together, our findings demonstrated that Z86 suppressed TGF-β induced pulmonary fibrosis in A549 and HFL cells and BLM induced pulmonary fibrotic mice through inhibiting TGF-β/Smad2/3 signaling, and provided the possibility of USP15 inhibitors as the potential drug candidates for idiopathic pulmonary fibrosis.

Indexed as

Pulmonary fibrosisSmad2/3TGF-βUSP15Z86

Identifiers

PMID42663780
PMCPMC13524897

What Socratic holds

Textmetadata
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 Socratic graph.