2. Apoptosis
  3. Bcl-2 Family
  4. S63845

S63845 est un inhibiteur puissant et sélectif de la leucémie myéloïde 1 (MCL1) avec un Kd de 0,19 nM pour MCL1 humain.

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
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 274 In-stock
Solution
10 mM * 1 mL in DMSO USD 274 In-stock
Solid
1 mg USD 96 In-stock
5 mg USD 180 In-stock
10 mg USD 300 In-stock
25 mg USD 540 In-stock
50 mg USD 780 In-stock
100 mg USD 1440 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 72 publication(s) in Google Scholar

Other Forms of S63845:

S63845 Related Antibodies

Top Publications Citing Use of Products

69 Publications Citing Use of MCE S63845

WB
Cell Viability Assay

    S63845 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2020 Jun 8;11(6):443.  [Abstract]

    In A375 cells, knockdown (KD) of MCL1 (shMCL1), BCL2 (shBCL2), BCLW (shBCLW), and BCLXL (shBCLXL) lines are created by shRNA technology. shBCLXL (in presence of S63845) shows significant reduction in cell viability during 48 h drug treatment.

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

    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 MedChemExpress. Usage Cited in: Clin Res Hepatol Gas. 2019 Jun;43(3):292-300.  [Abstract]

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

    View All Bcl-2 Family Isoform Specific Products:

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    Bcl-2 Bcl-xL Bcl-W Mcl-1 Bfl-1 Bcl-B Bax Bak Bim

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

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

    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].

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

    S63845 Related Antibodies
    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].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Molecular Weight

    829.26

    Formula

    C39H37ClF4N6O6S
    CAS No.
    Appearance

    Solid

    Color

    White to yellow

    SMILES

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

    Room temperature in continental US; may vary elsewhere.
    Storage

    4°C, protect from light, stored under nitrogen

    *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

    Solvent & Solubility
    In Vitro: 

    DMSO : 33.33 mg/mL (40.19 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

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

      Solubility: ≥ 2.08 mg/mL (2.51 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

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

      Solubility: ≥ 2.08 mg/mL (2.51 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  50% PEG300    50% Saline

      Solubility: 5 mg/mL (6.03 mM); Clear solution; Need ultrasonic

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

    *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.94%

    COA (263 KB) HNMR (201 KB) LCMS (675 KB)

    Handling Instructions (2659 KB)
    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

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.2059 mL 6.0295 mL 12.0589 mL 30.1474 mL
    5 mM 0.2412 mL 1.2059 mL 2.4118 mL 6.0295 mL
    10 mM 0.1206 mL 0.6029 mL 1.2059 mL 3.0147 mL
    15 mM 0.0804 mL 0.4020 mL 0.8039 mL 2.0098 mL
    20 mM 0.0603 mL 0.3015 mL 0.6029 mL 1.5074 mL
    25 mM 0.0482 mL 0.2412 mL 0.4824 mL 1.2059 mL
    30 mM 0.0402 mL 0.2010 mL 0.4020 mL 1.0049 mL
    40 mM 0.0301 mL 0.1507 mL 0.3015 mL 0.7537 mL
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    S63845 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    S638451799633-27-4S 63845S-63845Bcl-2 FamilyInhibitorinhibitorinhibit

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