1. Apoptosis
  2. Bcl-2 Family

A-1210477 

Cat. No.: HY-12468 Purity: 98.89%
Data Sheet SDS Handling Instructions

A-1210477 is a potent and selective inhibitor of MCL-1, and weakly binds to BCL-2 and BCL-XL, with Ki of 0.45 nM, 132 nM and >660 nM, respectively.

For research use only. We do not sell to patients.
A-1210477 Chemical Structure

A-1210477 Chemical Structure

CAS No. : 1668553-26-1

Size Price Stock Quantity
5 mg $60 In-stock
10 mg $110 In-stock
50 mg $400 In-stock
100 mg $650 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

    A-1210477 purchased from MCE. Usage Cited in: Open Biol. 2016 Aug;6(8). pii: 160134.

    Immunoblots showing affinity purification of GFP-tagged Mcl-1 in the presence of 2 μM A-1210477, and detection of co-purifying Bak.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    A-1210477 is a potent and selective inhibitor of MCL-1, and weakly binds to BCL-2 and BCL-XL, with Ki of 0.45 nM, 132 nM and >660 nM, respectively.

    IC50 & Target

    Ki: 0.45 nM (MCL-1), 132 nM (BCL-2), >660 nM (BCL-XL)[1]

    In Vitro

    A-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[1]. 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[3]. A-1210477 (0, 5, 10 and 15 μM) has minimal effect on cell viability but substantially sensitizes resistant BCL2High NHL cell lines to navitoclax[4].

    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 1.1764 mL 5.8821 mL 11.7642 mL
    5 mM 0.2353 mL 1.1764 mL 2.3528 mL
    10 mM 0.1176 mL 0.5882 mL 1.1764 mL
    Kinase Assay
    [1]

    TR-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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    A-1210477 is dissolved in DMSO.

    Adherent 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    850.04

    Formula

    C₄₆H₅₅N₇O₇S

    CAS No.

    1668553-26-1

    Storage

    Please store the product under the recommended conditions in the Certificate of Analysis.

    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: < 4.8 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    A-1210477
    Cat. No.:
    HY-12468
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