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    FLI-06
    FLI-06

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0722
    CAS #: 313967-18-9Purity ≥98%

    Description: FLI-06 (FLI 06; FLI-06) is a novel and potent inhibitor of Notch signaling pathway with EC50 of 2.3 μM. Notch is a receptor that is able to mediate intercellular signaling through a pathway conserved across the metazoa. It is involved in cell fate assignation and pattern formation during development. 

    References: Nat Chem Biol. 2013 Nov;9(11):731-8.

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    Molecular Weight (MW)438.52
    FormulaC25H30N2O5
    CAS No.313967-18-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 88 mg/mL (200.7 mM)
    Water: <1 mg/mL
    Ethanol: 8 mg/mL (18.2 mM)
    Other infoChemical Name: cyclohexyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
    InChi Key: SWWVFYHSSOWZMF-UHFFFAOYSA-N
    InChi Code: InChI=1S/C25H30N2O5/c1-15-21(24(29)32-18-7-5-4-6-8-18)22(16-9-11-17(12-10-16)27(30)31)23-19(26-15)13-25(2,3)14-20(23)28/h9-12,18,22,26H,4-8,13-14H2,1-3H3
    SMILES Code: O=C(C1=C(C)NC2=C(C(CC(C)(C)C2)=O)C1C3=CC=C([N+]([O-])=O)C=C3)OC4CCCCC4
    SynonymsFLI 06; FLI-06; FLI06; 


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    In Vitro

    In vitro activity:In HeLa NotchΔE-eGFP cells, FLI-06 blocks Notch trafficking and processing. FLI-06 changes the maturation pattern of APP and abolishes the shedding of APPs in HEK293 cells stably expressing a mutated APP that yields robust amounts of amyloid β. FLI-06 disrupt the Golgi apparatus, and inhibits general secretion at a step before exit from the endoplasmic reticulum (ER), which is accompanied by a tubule-to-sheet morphological transition of the ER.


    Kinase Assay: EC50 values of the test compounds are calculated from serial dilution series ranging from 200 to 0.1 μM. Cells are seeded in 96-well plates at a density of 5,000 cells per well in 100 μL medium. The next day, 100 μL medium containing each test compound is added. Cells are incubated for 16 h, fixed and processed for automated microscopy. EC50 estimates are calculated using four-parameter log-logistic fit with the package drc.


    Cell Assay: Treatment of HeLa NotchΔE-eGFP cells with FLI-06 resulted in accumulation of NotchΔE-eGFP and reduced NICD-eGFP production. The phenotype was fully reversible within 1–4 h when washing out of FLI-06, which indicated that FLI-06 is not acutely toxic in cells [1]. In FLI-06 treated cells, Aβ secretion reduced significantly but not APPCTF accumulation, suggesting that FLI-06 acts upstream of α-secretase and β-secretase cleavage. Immunofluorescence analysis of HeLa cells revealed that FLI-06 caused a complete disruption of the Golgi, which can be caused by interfering with membrane trafficking in the early secretory pathway or by disassembly of the microtubules17. FLI-06 inhibited ER exit and also elicited the tubule-to-sheet phenotype, which are related to each other

    In VivoFLI-06 (50 μM) inhibits endogenous Notch signaling in zebrafish embryos.
    Animal modelzebrafish
    Formulation & Dosage50 μM
    ReferencesNat Chem Biol. 2013 Nov;9(11):731-8.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

     

    FLI-06

    Nat Chem Biol. 2013 Nov;9(11):731-8.
     

    FLI-06

    Nat Chem Biol. 2013 Nov;9(11):731-8.
     

    FLI-06

    Nat Chem Biol. 2013 Nov;9(11):731-8.
     

    FLI-06

    Nat Chem Biol. 2013 Nov;9(11):731-8.
     

    FLI-06

    Nat Chem Biol. 2013 Nov;9(11):731-8.


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