Discover Community Create You

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Article

Discovery of a covalent FGFR2-selective inhibitor overcoming clinically-acquired resistance mutations.

Nature communications - 3 Aug 2026

Huang Xiaohao, Cao Xiansheng, Zheng Lulu, Luo Ruixiang, Fang Zhenglan, Liang Yongling, Zhu Yongjuan, Chen Shiyan, Zheng Lei, Xu Zheng, Li Xiaokun, Liang Guang, Chen Lingfeng

Abstract excerpt

Abnormal activation of fibroblast growth factor receptor 2 (FGFR2) drives tumorigenesis in various cancers. Clinical use of pan-FGFR inhibitors is limited due to emerging acquired resistance mutations within the FGFR2 kinase domain and adverse effects associated with FGFR1/4 off-target inhibition. Herein, we describe the structure-based discovery of LC-F2-1, an FGFR2-selective inhibitor that demonstrates...

Read the complete abstract on PubMed

Topics

Receptor, Fibroblast Growth Factor, Type 2
Humans
Animals
Mutation
Drug Resistance, Neoplasm
Crystallography, X-Ray

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Protein Kinase Inhibitors

Mice

Cell Line, Tumor

Xenograft Model Antitumor Assays

Female

Signal Transduction

Source

Open in PubMed Open full text

Identifiers

PMID: 42675086
DOI: 10.1038/s41467-026-76339-0
PMCID: PMC13530216

Genes

FGFR2
F2
FGFR1
FGFR4

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 25 Oct 2026.

Related research

Semantic proximity does not establish scientific evidence. Graph snapshot: 2026-09-29.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

Discovery of a covalent FGFR2-selective inhibitor overcoming clinically-acquired resistance mutations.PMID 42675086Read ↗

Design, synthesis and antitumor activity of a novel FGFR2-selective degrader to overcome resistance of the FGFR2V564F gatekeeper mutation based on a pan-FGFR inhibitor.Semantic proximity Read ↗

Structure-Based Design of a Novel Covalent 4-(1-Methylindol-3-yl)pyrimidin-2-amine Series Targeting FGFR2 Resistance Mutations.Semantic proximity Read ↗

RLY-4008, the First Highly Selective FGFR2 Inhibitor with Activity across FGFR2 Alterations and Resistance Mutations.Semantic proximity Read ↗

Illuminating the molecular mechanisms of tyrosine kinase inhibitor resistance for the FGFR1 gatekeeper mutation: the Achilles' heel of targeted therapy.Semantic proximity Read ↗

Selective FGFR/FGF pathway inhibitors: inhibition strategies, clinical activities, resistance mutations, and future directions.Semantic proximity Read ↗

Discovery of KIN-3248, An Irreversible, Next Generation FGFR Inhibitor for the Treatment of Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations.Semantic proximity Read ↗

The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations.Semantic proximity Read ↗

Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use.Semantic proximity Read ↗

FGFR-TKI resistance in cancer: current status and perspectives.Semantic proximity Read ↗

Mechanisms of clinical resistance to selective FGFR2 inhibition by lirafugratinib.Semantic proximity Read ↗

DFG-out mode of inhibition by an irreversible type-1 inhibitor capable of overcoming gate-keeper mutations in FGF receptors.Semantic proximity Read ↗

The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinomaSemantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.