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    BIOMARKER:

    FGFR4 V550L

    i
    Other names: FGFR4, CD334, JTK2, Fibroblast growth factor receptor 4
    Entrez ID:
    2264
    Related biomarkers:
    Expression
    Mutation
    CNA
    9ms
    Discovery of 6-Formylpyridyl Urea Derivatives as Potent Reversible-Covalent Fibroblast Growth Factor Receptor 4 Inhibitors with Improved Anti-Hepatocellular Carcinoma Activity. (PubMed, J Med Chem)
    Furthermore, 8z displayed desirable microsomal stability and significant in vivo efficacy in the Huh7 HCC cancer xenograft model in nude mice. The study provides a promising new lead for anticancer drug discovery directed toward overcoming FGFR4 gatekeeper mutation mediated resistance in HCC patients.
    Journal
    |
    FGF19 (Fibroblast growth factor 19) • FGFR4 (Fibroblast growth factor receptor 4)
    |
    FGFR4 mutation • FGFR4 V550L
    over1year
    Design, synthesis and biological evaluation of indazole derivatives as selective covalent inhibitors of FGFR4 in wild-type and gatekeeper mutants. (PubMed, Eur J Med Chem)
    Meanwhile, compound 27i exhibited potent antitumor potency (TGI: 83.0%, 40 mg/kg, BID) in Huh7 xenograft mouse models with no obvious toxicity observed. Overall, compound 27i was identified as a promising preclinical candidate for overcoming FGFR4 gatekeeper mutations for HCC treatment.
    Journal
    |
    ETV6 (ETS Variant Transcription Factor 6) • FGF19 (Fibroblast growth factor 19) • FGFR4 (Fibroblast growth factor receptor 4)
    |
    FGFR4 mutation • FGFR4 V550L
    over1year
    Discovery & characterization of a next-generation FGFR4 inhibitor overcoming resistant mutations (AACR 2023)
    Efficacy studies were conducted in HCC xenograft models and mutant FGFR4-dependent xenograft models including a RMS PDX model harboring FGFR4 V550L mutation. ABSK012 demonstrated strong potency over multiple FGFR4 mutants that are insensitive to a first generation FGFR4 inhibitor BLU-554. ABSK012, presented here by Abbisko Therapeutics, is a highly potent, selective, and next-generation small molecule FGFR4 inhibitor overcoming FGFR4 mutations resistant to first-generation inhibitors. Its superior preclinical profile supports its fast-track development into clinic.
    Late-breaking abstract
    |
    FGF19 (Fibroblast growth factor 19) • FGFR4 (Fibroblast growth factor receptor 4) • AVEN (Apoptosis And Caspase Activation Inhibitor)
    |
    FGF19 overexpression • FGFR4 mutation • FGFR4 V550L • FGFR wild-type
    |
    fisogatinib (BLU-554) • ABSK012