1. Apoptosis
  2. Bcl-2 Family

S63845 

Cat. No.: HY-100741 Purity: 99.94%
Handling Instructions

S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a Kd of 0.19 nM for human MCL1.

For research use only. We do not sell to patients.

S63845 Chemical Structure

S63845 Chemical Structure

CAS No. : 1799633-27-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 274 In-stock
Estimated Time of Arrival: December 31
1 mg USD 96 In-stock
Estimated Time of Arrival: December 31
5 mg USD 180 In-stock
Estimated Time of Arrival: December 31
10 mg USD 300 In-stock
Estimated Time of Arrival: December 31
25 mg USD 540 In-stock
Estimated Time of Arrival: December 31
50 mg USD 780 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1440 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

    S63845 purchased from MCE. Usage Cited in: Clin Cancer Res. 2018 Nov 1;24(21):5458-5470.

    Primary LuCaP35CR and LuCaP70CR cultures are treated with ABT-263 alone, S63845 alone, or combination for 4 hours in 2D culture. The cell lysates then are immunoblotted for indicated proteins.

    S63845 purchased from MCE. Usage Cited in: Clin Res Hepatol Gas. 2018. Dec.

    S63845 and A-1210477 trigger apoptosis signaling and reduce the levels of putative stem biomarkers in HCC cell lines.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a Kd of 0.19 nM for human MCL1.

    IC50 & Target[1]

    MCL1

    0.19 nM (Kd)

    In Vitro

    The pro-survival protein myeloid cell leukemia 1 (MCL1) is over expressed in many cancers. S63845 is a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. The activity of S63845 is next evaluated in a panel of eight AML cell lines: all lines are sensitive to S63845 (IC50=4-233 nM)[1].

    In Vivo

    S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Intravenously injected (i.v.) S63845 exerts dose-dependent anti-tumour activity in human multiple myeloma (H929 and AMO1) xenografts in immunocompromised mice, with maximal tumour growth inhibition of 114% in the AMO1 model and 103% in the H929 model. At 25 mg/kg, S63845 induces complete regression in 7 out of 8 of the mice at 100 days after treatment in the AMO1 model[1].

    Solvent & Solubility
    In Vitro: 

    DMSO : 33.33 mg/mL (40.19 mM; Need ultrasonic)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.2059 mL 6.0295 mL 12.0589 mL
    5 mM 0.2412 mL 1.2059 mL 2.4118 mL
    10 mM 0.1206 mL 0.6029 mL 1.2059 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.25 mg/mL (2.71 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: 2.25 mg/mL (2.71 mM); Suspended solution; Need ultrasonic

    • 3.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.25 mg/mL (2.71 mM); Clear solution

    References
    Kinase Assay
    [1]

    10 mM HEPES pH 7.4, 175 mM NaCl, 25 μM EDTA, 1 mM TCEP, 0.01% P20 and 1% DMSO is used as a running buffer. The ligand surface is generated using double His-tagged proteins. Serial dilutions of the compound in buffer are injected over the protein surface. All sample measurements are performed at a flow rate of 30 μL per min (injection time 120 s, dissociation time 360 s). The sensor surface is regenerated by consecutive injections of 0.35 M EDTA pH 8.0 with 0.1 mg/mL trypsin, 0.5 M imidazole and 45% DMSO (60 s, 15 μL per min)[1].

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

    Cell Assay
    [1]

    Cells are treated with increasing doses of S63845 (typically 0.008, 0.025, 0.04, 0.2, 1, 5 μM) for 24 h. Cells are stained with Annexin V-FITC and propidium iodide, analysed on a FACS Calibur and live cells are recorded. Data are presented as per cent cell death induction relative to cells cultured in medium alone[1].

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

    Animal Administration
    [1]

    Mice: S63845 is formulated extemporaneously in 25 mM HCl, 20% 2-hydroxy propyl β -cyclo dextrin 20% and administrated at the 6.25, 12.5, 25 mg/kg for 0, 20, 40, 60, 80 days. Tumour growth inhibition (TGImax) is calculated[1].

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

    References
    Molecular Weight

    829.26

    Formula

    C₃₉H₃₇ClF₄N₆O₆S

    CAS No.

    1799633-27-4

    SMILES

    CC(C(Cl)=C(OCCN1CCN(C)CC1)C=C2)=[[email protected]@]2[[email protected]]3=C(C4=CC=C(F)O4)SC5=NC=NC(O[[email protected]](CC6=C(OCC7=CC=NN7CC(F)(F)F)C=CC=C6)C(O)=O)=C53

    Storage

    4°C, stored under nitrogen

    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.94%

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    Inquiry Information

    Product Name:
    S63845
    Cat. No.:
    HY-100741
    Quantity:

    S63845

    Cat. No.: HY-100741