Evidence map›Paper›PMID 42232344›Full record

ArticlePharmaceutical science advances2026

Discovery of novel Kir4.1 inhibitors based on serdemetan with potential therapy for glioblastoma-depression comorbidity.

Hao Gu, Sisi Wang, Mengdan Li, Yunpeng Guo, Xiaokang Li, Zhaobing Gao, Jian Li, Hanfang Liu, Xiaoyu Zhou, Yixiang Xu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutical science advances, 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

10 authors.

Hao GuState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Sisi WangState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Mengdan LiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Yunpeng GuoState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Xiaokang LiState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Zhaobing GaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Jian LiState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Hanfang LiuCenter for Translational Medicine, Huaihe Hospital of Henan University, Kaifeng, 475004, China.
Xiaoyu ZhouState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Yixiang XuState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Primary gliomas frequently accompany depression, worsening symptoms and prognosis. Current combination therapies show limited efficacy due to poor compliance, overlapping adverse effects, and delayed antidepressant onset. To address this challenge, we aimed to develop a bifunctional agent with both antiglioma and antidepressant properties. Targeting astrocytic Kir4.1 (Kir4.1 potassium channel) in the lateral habenula has been proposed as a potential therapeutic strategy for depression, with the advantage of rapid-onset effects. Through high-throughput screening, Serdemetan (Serd), a broad-spectrum antitumor agent currently in phase I clinical trials with potent antiglioma activity, was found to exhibit moderate Kir4.1 inhibitory activity. Based on this, Serd was selected as the bifunctional lead compound. A series of structural modifications were carried out to enhance its inhibitory activity against Kir4.1 while retaining its antiglioma efficacy, resulting in 21 novel derivatives. Among these, compound

Indexed as

AntidepressionAntigliomaBifunctional compoundKir4.1 inhibitorsStructural repurposing

Identifiers

PMID42232344
PMCPMC13224378

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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.