Evidence mapPaperPMID 42181886Full record

ArticleFrontiers in pharmacology2026

Gamma-glutamyl metformin inhibits renal cell carcinoma progression by activating AMPK signaling pathway.

Zheng Lv, Li Song Zhang, Awuti Aisha, Tian Hang Wang, Hai Yan Cui, Shuai Tang, Jiang Hui Zhang, Fan Chang, Wen Song Wu, Lu Yuan Li and 2 more

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 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

12 authors.

Zheng Lv *Department of Urology, Central Hospital, Tianjin University/Tianjin Third Central Hospital, Tianjin, China.
Li Song Zhang *State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Awuti AishaThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Tian Hang WangState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Hai Yan CuiState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Shuai TangDepartment of Urology, Central Hospital, Tianjin University/Tianjin Third Central Hospital, Tianjin, China.
Jiang Hui ZhangDepartment of Urology, Central Hospital, Tianjin University/Tianjin Third Central Hospital, Tianjin, China.
Fan ChangDepartment of Urology, Central Hospital, Tianjin University/Tianjin Third Central Hospital, Tianjin, China.
Wen Song WuDepartment of Urology, Affiliated Hospital of Jianghan University, Wuhan, China.
Lu Yuan LiState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Zhi Song ZhangTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.
Fang Min ChenDepartment of Urology, Central Hospital, Tianjin University/Tianjin Third Central Hospital, Tianjin, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin is a promising candidate for the treatment of renal cell carcinoma (RCC), and elucidating its anti-tumor mechanisms is of great clinical significance. Overexpression of Gamma-glutamyl transpeptidase (GGT) in RCC tissues has been identified as a potential biomarker for renal cell tumors. Thus, there is an urgent need to develop a metformin prodrug that leverages the overexpression specificity of GGT in RCC tissues to achieve targeted release of metformin for RCC therapy. Herein, we innovatively report the development and the antitumor activity of gamma-Glutamyl Metformin (γE-Met), which exerts its effects by activating AMP-activated protein kinase (AMPK) signaling pathway. Compared with metformin, γE-Met specifically releases free metformin in renal cancer cells under the catalysis of GGT, thereby prolonging the retention time of metformin in tumor cells and more effectively inhibiting the growth and metastasis of renal cancer cells. Our experimental results demonstrate that GGT-responsive γE-Met can significantly enhance the therapeutic efficacy of metformin, rendering it a promising metformin prodrug with substantial clinical application prospects.

Indexed as

AMPK signaling pathwaygamma-glutamyl transpeptidasemetforminprodrugrenal cancer

Identifiers

PMID42181886
PMCPMC13189888

What Socratic holds

Textmetadata
LicenceCC BY
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.