Evidence map›Paper›PMID 42482266›Full record

ArticleJournal of translational medicine2026

AI-Driven discovery and experimental validation of covalent FGFR4 inhibitors for hepatocellular carcinoma.

Mingjie Gao, Weiyi Zhao, Pengfei Zhang, Mengmeng Pei, Zhenyu Zhang, Min Chen, Bin Han, Xuemei Chen, Biao Ni, Jiawei Yang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

13 authors.

Mingjie Gao *Shandong Provincial Key Medical and Health Laboratory of BT and IT for Thoracic Oncology, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China.
Weiyi Zhao *Department of Neurosurgery, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China.
Pengfei Zhang *Key Laboratory of Molecular Pharmacology and Translational Research, School of Pharmacy, Shandong Second Medical University, Weifang, Shandong, 261053, People's Republic of China.
Mengmeng Pei *Health Management Center, Weifang People's Hospital, Weifang, Shandong, 261041, People's Republic of China.
Zhenyu ZhangShandong Provincial Key Medical and Health Laboratory of BT and IT for Thoracic Oncology, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China.
Min ChenDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, China.
Bin HanDepartment of Neurosurgery, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China.
Xuemei ChenSchool of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Biao NiDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, China.
Jiawei YangShandong Provincial Key Medical and Health Laboratory of BT and IT for Thoracic Oncology, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China.
Zengwu WangDepartment of Neurosurgery, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China. wangzengwu70@sina.com.
Xiaolong DuDepartment of Neurosurgery, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China. dxiaolong52@163.com.
Shaoqiang WangShandong Provincial Key Medical and Health Laboratory of BT and IT for Thoracic Oncology, Weifang People's Hospital, Shandong Second Medical University, Guangwen Street, Weifang, Shandong, 261041, People's Republic of China. rmyywsq227@sdsmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFGFR4 signaling is an essential driver in hepatocellular carcinoma. However, traditional screening is often time-consuming, highlighting a need for efficient strategies to identify covalent chemotypes and accelerate FGFR4 drug discovery.

methodsWe established an integrated AI-driven virtual screening framework to discover FGFR4 covalent inhibitors. The theoretical predictions were evaluated through a biochemical pipeline, encompassing in vitro FGFR4 kinase assays, immunoblotting of intracellular signaling cascades, and bottom-up LC-MS/MS peptide mapping.

resultsBiological validation of the computational predictions identified five distinct chemical scaffolds (hits 1, 2, 5, 7, and 8) exhibiting antiproliferative activity. The two most active candidates, hit 1 and hit 2, were selected for further mechanistic profiling. These compounds demonstrated dose-dependent FGFR4 kinase inhibition with IC

conclusionsOur AI-guided computational workflow identified multiple covalent FGFR4 inhibitors with measurable biological activity. Hit 1 and hit 2 represent structurally characterized covalent scaffolds. This study provides chemical starting points for targeted HCC therapy and demonstrates the integration of theoretical prediction and experimental validation in covalent drug discovery.

Indexed as

Carcinoma, HepatocellularDrug DiscoveryLiver NeoplasmsProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 4Cell Line, TumorCell ProliferationHumansPhosphorylationReproducibility of ResultsSignal TransductionTandem Mass SpectrometryFGFR4 protein, humanProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 4AI-Driven screeningFGFR4 covalent inhibitorsHepatocellular carcinomaKinase inhibitionLC-MS/MS validation

Identifiers

PMID42482266
PMCPMC13452133

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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.