ArticleCommunications chemistry2022
Structure-based design of a dual-warhead covalent inhibitor of FGFR4.
Article in Communications chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- The role of FGF19-FGFR4 signaling pathway in liver health and disease: Guardian or destroyer.Genes & diseases · 2026Review
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- AI-Driven discovery and experimental validation of covalent FGFR4 inhibitors for hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Acquisition of a novel restriction modification system regulates genetic flux and gene expression in the hypervirulent and globally disseminated CC17 lineage of group B Streptococcus.Nucleic acids research · 2026Article
- Fibroblast growth factor 19-fibroblast growth factor receptor 4 axis: From oncogenesis to targeted-immunotherapy in advanced hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Covalent chemical probes.Communications chemistry · 2025Article
- Exploring Extended Warheads toward Developing Cysteine-Targeted Covalent Kinase Inhibitors.Journal of chemical information and modeling · 2024Article
- Molecular Bidents with Two Electrophilic Warheads as a New Pharmacological Modality.ACS central science · 2024Article
- Redox takes control.eLife · 2024Article
- Covalent targeting of non-cysteine residues in PI4KIIIβ.RSC chemical biology · 2023Article
- Reversible Dual-Covalent Molecular Locking of the 14-3-3/ERRγ Protein-Protein Interaction as a Molecular Glue Drug Discovery Approach.Journal of the American Chemical Society · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) signaling pathways play critical roles in a variety of cancers, such as hepatocellular carcinoma (HCC). FGFR4 is recognized as a promising target to treat HCC. Currently, all FGFR covalent inhibitors target one of the two cysteines (Cys477 and Cys552). Here, we designed and synthesized a dual-warhead covalent FGFR4 inhibitor, CXF-009, targeting Cys477 and Cys552 of FGFR4. We report the cocrystal structure of FGFR4 with CXF-009, which exhibits a dual-warhead covalent binding mode. CXF-009 exhibited stronger selectivity for FGFR4 than FGFR1-3 and other kinases. CXF-009 can also potently inhibit the single cystine mutants, FGFR4(C477A) and FGFR4(C552A), of FGFR4. In summary, our study provides a dual-warhead covalent FGFR4 inhibitor that can covalently target two cysteines of FGFR4. CXF-009, to our knowledge, is the first reported inhibitor that forms dual-warhead covalent bonds with two cysteine residues in FGFR4. CXF-009 also has the potential to overcome drug induced resistant FGFR4 mutations and might serve as a lead compound for future anticancer drug discovery.
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Registered trials
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.