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    BIOMARKER:

    FLT3-ITD mutation + FLT3 D835Y + FLT3 F691L

    i
    Other names: FLT3, Fms Related Tyrosine Kinase 3, Receptor-Type Tyrosine-Protein Kinase FLT3, Stem Cell Tyrosine Kinase 1, Fms-Like Tyrosine Kinase 3, CD135, FLK-2, STK1, Growth Factor Receptor Tyrosine Kinase Type III, Fetal Liver Kinase 2
    Entrez ID:
    2322
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    6ms
    Structure-Based Optimization of Pyrazinamide-Containing Macrocyclic Derivatives as Fms-like Tyrosine Kinase 3 (FLT3) Inhibitors to Overcome Clinical Mutations. (PubMed, ACS Pharmacol Transl Sci)
    Furthermore, 8v demonstrated ideal anticancer efficacy in a Ba/F3-FLT3-ITD-D835Y xenograft model. The results suggested that 8v can serve as a promising macrocycle-based FLT3 inhibitor for the treatment of AML.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation • FLT3 D835Y • FLT3 F691L • FLT3 D835 • FLT3-ITD mutation + FLT3 D835Y + FLT3 F691L
    1year
    BGS-2456 Is a Novel Potent Covalent Inhibitor of FLT3 That Highly Discriminates Against KIT and Is Not Toxic Toward Normal Hematopoiesis in Vitro (ASH 2023)
    While there are numerous examples of KIT TKIs that do not inhibit FLT3 (imatinib, avapritinib, dasatinib), to date, all clinically active FLT3 TKIs (quizartinib, gilteritinib, midostaurin, sorafenib) fail to spare KIT inhibition...Compared to FF-10101 and gilteritinib, BGS-2456 exhibited the least amount of hematologic toxicity, facilitating in vitro proliferation and differentiation of normal hematopoietic progenitor cells even at 100x EC50 concentration against Molm14 cells... This is the first description of a potent and exquisitely specific FLT3 inhibitor that spares KIT inhibition and displays no myelosuppression in vitro at >100x EC50 concentration. The potent inhibitory effects of BGS-2456 on both D835Y and F691L mutants support its promise as a best-in-class TKI for the treatment of FLT3-mutant AML. Efforts to molecularly dissect the basis of the high degree of selectivity of BGS-2456 are ongoing.
    Preclinical
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    FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CSF1R (Colony stimulating factor 1 receptor)
    |
    FLT3-ITD mutation • FLT3 mutation • KIT mutation • FLT3 D835Y • FLT3 F691L • FLT3 D835 • PDGFRA mutation • FLT3 D835V • FLT3 F691L + FLT3 D835V • FLT3-ITD mutation + FLT3 D835Y + FLT3 F691L
    |
    dasatinib • sorafenib • imatinib • Xospata (gilteritinib) • Rydapt (midostaurin) • Vanflyta (quizartinib) • Ayvakit (avapritinib) • FF-10101 • BGS-2456