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    A-1210477
    A-1210477

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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 #: V0010
    CAS #: 1668553-26-1Purity ≥98%

    Description: A-1210477 is a novel, potent and specific MCL-1 (Myeloid cell leukemia-1) inhibitor with Ki and IC50 of 0.45 nM and 26.2 nM, respectively. In MCL-1-dependent SVEC cells, treatment with A-1210477 at varying doses, induced cell death in a dose-dependent manner. SYTOX Green exclusion and live-cell imaging were used to determine cell viability. In line with increased potency, cell death was more rapidly induced by A-1210477. To examine the selectivity of A-1210477 for targeting Bcl-2 family members, BcL-xL-, BcL-2-, and MCL-1-dependent SVEC cells were treated with A-1210477. A-1210477 only killed MCL-1-dependent cells. Compared with UMI-77, A-1210477 showed greater potency and specificity as an MCL-1 inhibitor, the EC50 value of UMI-77 is 10 µmol/L.

    References: Nat Commun. 2016 Feb 2;7:10538. 


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    Molecular Weight (MW)850.04
    FormulaC46H55N7O7S
    CAS No.1668553-26-1
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 3 mg/mL (3.5 mM)
    Water: <1 mg/mL (slightly soluble or insoluble)
    Ethanol: <1 mg/mL
    SynonymsA-1210477; A 1210477; A1210477


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    In VitroA-1210477 (10 μM) reduces the amount of BIM co-immunoprecipitated with MCL-1 antibody, and triggers MCL-1 elevation in a variety of cancer cell lines, including the breast cancer cell line HCC-1806. A-1210477 inhibits MCL-1-NOXA interactions with an IC50 of approximately 1 μM, while having no effect on BCL-2-BIM or BCL-XL-BCL-XS interactions. The NSCLC cell lines H2110 and H23 are sensitive to A-1210477 with cell viability IC50<10 μM, confirming that A-1210477 can kill MCL-1-dependent cell lines. A-1210477 induces extensive concentration-dependent apoptosis in H929 cells following a brief (4 h) exposure. A-1210477 interacts with MCL-1 with Kd of appr 740 nM. A-1210477 (10 μM) induces extensive mitochondrial fragmentation in a DRP-1-dependent manner[2]. A-1210477 upregulates MCL-1 expression in BRAF-mutant CRC cells and in the melanoma cell line A375 in a dose-dependent manner. A-1210477 releases BAK from MCL-1 and cobimetinib induces BIM that is required for BAX activation. A-1210477 (0, 5, 10 and 15 μM) has minimal effect on cell viability but substantially sensitizes resistant BCL2High NHL cell lines to navitoclax. 
    Kinase AssayTR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride, and 1 mM DTT (pH 7.5) for BCL-XL.6 For MCL-1 assays, GST-tagged MCL-1 (1 nM) is mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters.
    Cell AssayAdherent cell lines are seeded at 50 000 cells per well in 96-well plates and treated for 48 h with compounds diluted in half-log steps starting at 30 μM and ending at 0.001 μM. Multiple myeloma cell lines are seeded at 15 000-20 000 cells per well and treated similarly. Effects on proliferation and viability are determined using CellTiter-Glo reagent from Promega according to the manufacturer's instructions. IC50 values are determined by non-linear regression analysis of the concentration response data.
    DosagesN/A
    AdministrationN/A
    ReferenceBlood Cancer J. 2015 Nov 13;5:e368


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

    A-1210477

    Loss of MCL-1 function modulates BAK expression. SKBR3 cells were treated with MCL-1 siRNA (#5), scrambled siRNA (Sc; both 20 nmol/L) or the MCL-1 inhibitor A-1210477 for 8 hours and the effect on MCL-1, PARP, and BAK determined by Western blot analysis (A) or by RT-PCR (B). Mol Cancer Ther October 1 2016 15 (10) 2273-2281

    A-1210477

    BCL-XL limits the efficacy of A-1210477 to a greater extent than BCL-2. SKBR3 cells overexpressing BCL-XL or BCL-2 were treated with A-1210477 for 24 hours and the percentage of apoptosis determined from the sub-G0–G1 DNA content of DNA cell-cycle histograms and compared with vector control (Vct Ctrl) or parental cell lines (wild-type, WT).

    A-1210477

    BIM redistribution mediated by loss in function of antiapoptotic BCL-2 proteins.


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