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> Molibresib [1260907-17-2]

Molibresib [1260907-17-2]

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Molibresib (I-BET762; GSK525762) is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

Para uso exclusivo en investigación. No vendemos a pacientes.

Molibresib Estructura química

Molibresib Estructura química

No. CAS : 1260907-17-2

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

Based on 20 publication(s) in Google Scholar

Other Forms of Molibresib:

  • I-BET762 carboxylic acid In-stock
  • GSK 525768A In-stock
  • Molibresib besylate In-stock

    Molibresib purchased from MedChemExpress. Usage Cited in: Nat Med. 2017 Sep;23(9):1055-1062.  [Abstract]

    Western blot of WCL of C4-2 cells treated with vehicle (DMSO) or different doses of JQ1 or i-BET for 24 h. Actin is used as a loading control.

    Molibresib purchased from MedChemExpress. Usage Cited in: Oncotarget. 2016 Jun 21;7(25):38319-38332.  [Abstract]

    iBET762 partially disrupts the interaction between full-length ERG and BRD4 (A), and between T1-E4 ERG and BRD4 (B).
    Descripciòn

    Molibresib (I-BET762; GSK525762) is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

    IC50 & Target

    IC50: 32.5-42.5 nM (BET)[1]
    In Vitro

    Molibresib (I-BET 762) shows the highest affinity interaction with BET. Molibresib binds to the tandem bromodomains of BET with high affinity (dissociation constant Kd of 50.5-61.3 nM). Molibresib displaces, with high efficacy (half-maximum inhibitory concentration IC50 of 32.5-42.5 nM), a tetra-acetylated H4 peptide that had been pre-bound to tandem bromodomains of BET[1]. Molibresib has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. Molibresib treatment leads to a reduction in the recruitment of all three proteins to chromatin[2]. Molibresib inhibits OPM-2 cell proliferation with IC50 of 60.15 nM[3].

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

    Molibresib Related Antibodies
    In Vivo

    The antimyeloma activity of Molibresib (I-BET 762) is tested dosed orally in an in vivo systemic xenograft model generated by injecting OPM-2 cells into NOD-SCID mice. Daily oral doses of Molibresib up to 10 mg/kg and 30 mg/kg given every other day are well tolerated with no clear impact on body weight compared with vehicle control. The plasma hLC concentration is significantly reduced in mice treated with Molibresib[3].

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

    423.90

    Fòrmula

    C22H22ClN5O2
    No. CAS

    1260907-17-2
    Appearance

    Solid

    Color

    Off-white to yellow

    SMILES

    ClC1=CC=C(C2=N[C@@H](CC(NCC)=O)C3=NN=C(C)N3C4=CC=C(OC)C=C24)C=C1
    Envío

    Room temperature in continental US; may vary elsewhere.
    Almacenamiento
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvente y solubilidad
    In Vitro: 

    DMSO : 200 mg/mL (471.81 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    1M HCl : 100 mg/mL (235.90 mM; ultrasonic and adjust pH to 1 with HCl)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.3590 mL 11.7952 mL 23.5905 mL
    5 mM 0.4718 mL 2.3590 mL 4.7181 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Calculadora de molaridad

    • Calculadora de dilución

    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: ≥ 2.5 mg/mL (5.90 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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:  5% DMSO    40% PEG300    5% Tween-80    50% Saline

      Solubility: ≥ 2.5 mg/mL (5.90 mM); Clear solution

    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).
    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.
    Pureza y Documentación

    Purity: 99.94%

    COA (253 KB) LCMS (95 KB)

    Instrucciones de manejo (2659 KB)
    Referencias

    • [1]. Nicodeme E, et al. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23.  [Content Brief]

      [2]. Asangani IA, et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014 Jun 12;510(7504):278-82.  [Content Brief]

      [3]. Chaidos A, et al. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762. Blood. 2014 Jan 30;123(5):697-705.  [Content Brief]

    Ensayo celular
    [2]

    VCaP, LNCaP, 22RV1, DU145 and PC3 prostate cancer cell lines are seeded in 96-well plates at 2000-10,000 cells/well (optimum density for growth) in a total volume of 100μL media containing 10% FBS. Serially diluted compounds in 100μL media are added to the cells 12hr later. Following 96 hr. incubation, cell viability is assessed by Cell-Titer GLO. The values are normalized and IC50 is calculated using GraphPad Prism software. For long-term colony formation assay, 10,000-50,000 cells/well are seeded in six-well plates and treated with either 100 nM or 500 nM of JQ1 or DMSO. After 12 days cells are fixed with methanol, stained with crystal violet and photographed. For colorimetric assays, the stained wells are treated with 500μL 10% acetic acid and the absorbance is measured at 560nm using a spectrophotometer[2].

    MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
    Administraciòn de animales
    [3]

    Mice[3]
    The antimyeloma efficacy of orally administered Molibresib is tested in a systemic xenograft myeloma model. For this purpose, sublethally irradiated (200 cGy) NOD/SCID mice age 9 to 11 weeks are given 107 OPM-2 myeloma cells via tail vein injection. On day 15 following inoculation, animals are started on oral treatment with Molibresib at escalating doses or vehicle (1% methylcellulose and 0.2% sodium lauryl sulfate), which is continued up to day 83. Specifically, 1 group of mice are treated with vehicle and 4 groups with different dosing schedules of Molibresib: 3 mg/kg per day; 10 mg/kg per day; 30 mg/kg on alternate days; and 30 to 20 mg/kg per day (ie, 30 mg/kg per day for 14 days, followed by 2 weeks [days 15 to 31] off treatment [drug is withheld due to a decline in body weight until animals has regained weight], follow by 20 mg/kg per day until termination of the experiment [days 43 to 82]). Blood samples (~70 μL) are removed at 0.5 hours after oral administration of Molibresib on day 15 (treatment initiation); days 27, 45, and 82 (3, 10, and 20 to 30 mg/kg once per day groups only); and day 83 (30 mg/kg once every other day group only). The blood is centrifuged to obtain 20 μL plasma and stored at -20°C prior to analysis for Molibresib by using a specific liquid chromatography/mass spectrometry/mass spectrometry assay.

    MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
    Referencias

    • [1]. Nicodeme E, et al. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23.  [Content Brief]

      [2]. Asangani IA, et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014 Jun 12;510(7504):278-82.  [Content Brief]

      [3]. Chaidos A, et al. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762. Blood. 2014 Jan 30;123(5):697-705.  [Content Brief]

    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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    1M HCl / DMSO 1 mM 2.3590 mL 11.7952 mL 23.5905 mL 58.9762 mL
    5 mM 0.4718 mL 2.3590 mL 4.7181 mL 11.7952 mL
    10 mM 0.2359 mL 1.1795 mL 2.3590 mL 5.8976 mL
    15 mM 0.1573 mL 0.7863 mL 1.5727 mL 3.9317 mL
    20 mM 0.1180 mL 0.5898 mL 1.1795 mL 2.9488 mL
    25 mM 0.0944 mL 0.4718 mL 0.9436 mL 2.3590 mL
    30 mM 0.0786 mL 0.3932 mL 0.7863 mL 1.9659 mL
    40 mM 0.0590 mL 0.2949 mL 0.5898 mL 1.4744 mL
    50 mM 0.0472 mL 0.2359 mL 0.4718 mL 1.1795 mL
    60 mM 0.0393 mL 0.1966 mL 0.3932 mL 0.9829 mL
    80 mM 0.0295 mL 0.1474 mL 0.2949 mL 0.7372 mL
    100 mM 0.0236 mL 0.1180 mL 0.2359 mL 0.5898 mL
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    Molibresib Related Classifications

    Help & FAQs

    Keywords:

    Molibresib1260907-17-2I-BET762 GSK525762 GSK525762AGSK525762GSK 525762GSK-525762Epigenetic Reader DomainInhibitorinhibitorinhibit

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